D E Hale

University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States

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Publications (114)619.88 Total impact

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    ABSTRACT: Surrogate measures are needed when recumbent length or height is unobtainable or unreliable. Arm span has been used as a surrogate but is not feasible in children with shoulder or arm contractures. Ulnar length is not usually impaired by joint deformities, yet its utility as a surrogate has not been adequately studied. In this cross-sectional study, we aimed to examine the accuracy and reliability of ulnar length measured by different tools as a surrogate measure of recumbent length and height. Anthropometrics [recumbent length, height, arm span, and ulnar length by caliper (ULC), ruler (ULR), and grid (ULG)] were measured in 1479 healthy infants and children aged <6 y across 8 study centers in the United States. Multivariate mixed-effects linear regression models for recumbent length and height were developed by using ulnar length and arm span as surrogate measures. The agreement between the measured length or height and the predicted values by ULC, ULR, ULG, and arm span were examined by Bland-Altman plots. All 3 measures of ulnar length and arm span were highly correlated with length and height. The degree of precision of prediction equations for length by ULC, ULR, and ULG (R(2) = 0.95, 0.95, and 0.92, respectively) was comparable with that by arm span (R(2) = 0.97) using age, sex, and ethnicity as covariates; however, height prediction by ULC (R(2) = 0.87), ULR (R(2) = 0.85), and ULG (R(2) = 0.88) was less comparable with arm span (R(2) = 0.94). Our study demonstrates that arm span and ULC, ULR, or ULG can serve as accurate and reliable surrogate measures of recumbent length and height in healthy children; however, ULC, ULR, and ULG tend to slightly overestimate length and height in young infants and children. Further testing of ulnar length as a surrogate is warranted in physically impaired or nonambulatory children.
    The Journal of nutrition. 07/2014;
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    ABSTRACT: The objective of this study was to characterize hearing loss in individuals with deletions of distal chromsome18q and to identify the smallest region of overlap of their deletions, thereby identifying potential causative genes. The clinical data were collected via a retrospective case study. Molecular data were obtained via high-resolution chromosome microarray analysis. The study was conducted as a component of the ongoing research protocols at the Chromosome 18 Clinical Research Center at the University of Texas Health Science Center at San Antonio. Thirty-eight participants with a deletion of the distal portion of the long arm of chromosome 18 were recruited to this study. The participants underwent an otologic examination as well as a basic audiometry evaluation. Blood samples were obtained, and high-resolution chromosome microarray analysis was performed. Pure tone averages and speech discrimination scores were determined for each participant. The region of hemizygosity for each participant was determined to within 2 Kb each of their breakpoints. Twenty-four participants (63%) had high-frequency hearing loss, similar to the pattern seen in presbycusis. Comparison of microarray results allowed identification of eight genes, including the candidate gene for dysmyelination (MBP). Individuals with a deletion of a 2.8 Mb region of 18q23 have a high probability (83%) of high-frequency sensorineural hearing loss.
    Otology & neurotology: official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology 03/2014; · 1.44 Impact Factor
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    ABSTRACT: Although constitutional chromosome abnormalities have been recognized since the 1960s, clinical characterization and development of treatment options have been hampered by their obvious genetic complexity and relative rarity. Additionally, deletions of 18q are particularly heterogeneous, with no two people having the same breakpoints. We identified 16 individuals with deletions that, despite unique breakpoints, encompass the same set of genes within a 17.6-Mb region. This group represents the most genotypically similar group yet identified with distal 18q deletions. As the deletion is of average size when compared with other 18q deletions, this group can serve as a reference point for the clinical and molecular description of this condition. We performed a thorough medical record review as well as a series of clinical evaluations on 14 of the 16 individuals. Common functional findings included developmental delays, hypotonia, growth hormone deficiency, and hearing loss. Structural anomalies included foot anomalies, ear canal atresia/stenosis, and hypospadias. The majority of individuals performed within the low normal range of cognitive ability but had more serious deficits in adaptive abilities. Of interest, the hemizygous region contains 38 known genes, 26 of which are sufficiently understood to tentatively determine dosage sensitivity. Published data suggest that 20 are unlikely to cause an abnormal phenotype in the hemizygous state and five are likely to be dosage sensitive: TNX3, NETO1, ZNF407, TSHZ1, and NFATC. A sixth gene, ATP9B, may be conditionally dosage sensitive. Not all distal 18q- phenotypes can be attributed to these six genes; however, this is an important advance in the molecular characterization of 18q deletions.
    Human Genetics 10/2013; · 4.63 Impact Factor
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    ABSTRACT: We examined 36 participants at least 4 years old with hemizygous distal deletions of the long arm of Chromosome 18 (18q-) for histories of mood disorders and to characterize these disorders clinically. Since each participant had a different region of 18q hemizygosity, our goal was also to identify their common region of hemizygosity associated with mood disorders; thereby identifying candidate causal genes in that region. Lifetime mood and other psychiatric disorders were determined by semi-structured interviews of patients and parents, supplemented by reviews of medical and psychiatric records, and norm-referenced psychological assessment instruments, for psychiatric symptoms, cognitive problems, and adaptive functioning. Sixteen participants were identified with lifetime mood disorders (ages 12-42 years, 71% female, 14 having had unipolar depression and 2 with bipolar disorders). From the group of 20 who did not meet criteria for a mood disorder; a comparison group of 6 participants were identified who were matched for age range and deletion size. Mood-disordered patients had high rates of anxiety (75%) and externalizing behavior disorders (44%), and significant mean differences from comparison patients (P < 0.05), including higher overall and verbal IQs and lower autistic symptoms. A critical region was defined in the mood-disordered group that included a hypothetical gene, C18orf62, and two known genes, ZADH2 and TSHZ1. We conclude that patients having terminal deletions of this critical region of the long arm of Chromosome 18 are highly likely to have mood disorders, which are often comorbid with anxiety and to a lesser extent with externalizing disorders. © 2013 Wiley Periodicals, Inc.
    American Journal of Medical Genetics Part B Neuropsychiatric Genetics 09/2013; · 3.23 Impact Factor
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    ABSTRACT: Pediatric metabolic syndrome (MS) and its cardiometabolic components (MSCs) have become increasingly prevalent, yet little is known about the genetics underlying MS risk in children. We examined the prevalence and genetics of MS-related traits among 670 non-diabetic Mexican American (MA) children and adolescents, aged 6-17 years (49 % female), who were participants in the San Antonio Family Assessment of Metabolic Risk Indicators in Youth study. These children are offspring or biological relatives of adult participants from three well-established Mexican American family studies in San Antonio, TX, at increased risk of type 2 diabetes. MS was defined as ≥3 abnormalities among 6 MSC measures: waist circumference, systolic and/or diastolic blood pressure, fasting insulin, triglycerides, HDL-cholesterol, and fasting and/or 2-h OGTT glucose. Genetic analyses of MS, number of MSCs (MSC-N), MS factors, and bivariate MS traits were performed. Overweight/obesity (53 %), pre-diabetes (13 %), acanthosis nigricans (33 %), and MS (19 %) were strikingly prevalent, as were MS components, including abdominal adiposity (32 %) and low HDL-cholesterol (32 %). Factor analysis of MS traits yielded three constructs: adipo-insulin-lipid, blood pressure, and glucose factors, and their factor scores were highly heritable. MS itself exhibited 68 % heritability. MSC-N showed strong positive genetic correlations with obesity, insulin resistance, inflammation, and acanthosis nigricans, and negative genetic correlation with physical fitness. MS trait pairs exhibited strong genetic and/or environmental correlations. These findings highlight the complex genetic architecture of MS/MSCs in MA children, and underscore the need for early screening and intervention to prevent chronic sequelae in this vulnerable pediatric population.
    Human Genetics 06/2013; · 4.63 Impact Factor
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    ABSTRACT: Preterm birth (PTB) is a complex trait, but little is known regarding its major genetic determinants. The objective of this study is to localize genes that influence susceptibility to PTB in Mexican Americans (MAs), a minority population in the United States (US), using predominantly microfilmed birth certificate-based data obtained from the San Antonio Family Birth Weight Study. Only 1,302 singleton births from 288 families with information on PTB and significant covariates were considered for genetic analysis. PTB is defined as a childbirth that occurs at <37 completed weeks of gestation, and the prevalence of PTB in this sample was 6.4%. An approximately 10 cM genetic map was used to conduct a genome-wide linkage analysis using the program SOLAR. The heritability of PTB was high (h(2)±SE: 0.75±0.20) and significant (P=4.5 x 10(-5)), after adjusting for the significant effects of birth weight and birth order. We found significant evidence for linkage of PTB (LOD=3.6; nominal P=2.3 x 10(-5); empirical P=1.0 x 10(-5)) on chromosome 18q between markers D18S1364 and D18S541. Several other chromosomal regions (2q, 9p, 16q, and 20q) were also potentially linked with PTB. A strong positional candidate gene in the 18q linked region is SERPINB2 or PAI-2, a member of the plasminogen activator system that is associated with various reproductive processes. In conclusion, to our knowledge, perhaps for the first time in MAs or US populations, we have localized a major susceptibility locus for PTB on chromosome 18q21.33-q23.
    Molecular Human Reproduction 05/2013; · 4.54 Impact Factor
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    ABSTRACT: Manolio et al. (Am J Epidemiol. 2012;175:859-866) proposed that large cohort studies adopt novel models using "temporary assessment centers" to enroll up to a million participants to answer research questions about rare diseases and "harmonize" clinical endpoints collected from administrative records. Extreme selection bias, we are told, will not harm internal validity, and "process expertise to maximize efficiency of high-throughput operations is as important as scientific rigor" (p. 861). In this article, we describe serious deficiencies in this model as applied to the United States. Key points include: 1) the need for more, not less, specification of disease endpoints; 2) the limited utility of data collected from existing administrative and clinical databases; and 3) the value of university-based centers in providing scientific expertise and achieving high recruitment and retention rates through community and healthcare provider engagement. Careful definition of sampling frames and high response rates are crucial to avoid bias and ensure inclusion of important subpopulations, especially the medically underserved. Prospective hypotheses are essential to refine study design, determine sample size, develop pertinent data collection protocols, and achieve alliances with participants and communities. It is premature to reject the strengths of large national cohort studies in favor of a new model for which evidence of efficiency is insufficient.
    American journal of epidemiology 01/2013; · 5.59 Impact Factor
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    ABSTRACT: Background:  The National Children's Study (NCS) was established as a national probability sample of births to prospectively study children's health starting from in utero to age 21. The primary sampling unit was 105 study locations (typically a county). The secondary sampling unit was the geographic unit (segment), but this was subsequently perceived to be an inefficient strategy. Methods and Results:  This paper proposes that second-stage sampling using prenatal care providers is an efficient and cost-effective method for deriving a national probability sample of births in the US. It offers a rationale for provider-based sampling and discusses a number of strategies for assembling a sampling frame of providers. Also presented are special challenges to provider-based sampling pregnancies, including optimising key sample parameters, retaining geographic diversity, determining the types of providers to include in the sample frame, recruiting women who do not receive prenatal care, and using community engagement to enrol women. There will also be substantial operational challenges to sampling provider groups. Conclusion:  We argue that probability sampling is mandatory to capture the full variation in exposure and outcomes expected in a national cohort study, to provide valid and generalisable risk estimates, and to accurately estimate policy (such as screening) benefits from associations reported in the NCS.
    Paediatric and Perinatal Epidemiology 01/2013; 27(1):20-26. · 2.16 Impact Factor
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    ABSTRACT: The goal of this study is to define the effects of TCF4 hemizygosity in the context of a larger segmental deletion of chromosome 18q. Our cohort included 37 individuals with deletions of 18q. Twenty-seven had deletions including TCF4 (TCF4 (+/-)); nine had deletions that did not include TCF4 (TCF4 (+/+)); and one individual had a microdeletion that included only the TCF4 gene. We compared phenotypic data from the participants' medical records, survey responses, and in-person evaluations. Features unique to the TCF4 (+/-) individuals included abnormal corpus callosum, short neck, small penis, accessory and wide-spaced nipples, broad or clubbed fingers, and sacral dimple. The developmental data revealed that TCF4 (+/+) individuals were only moderately developmentally delayed while TCF4 (+/-) individuals failed to reach developmental milestones beyond those typically acquired by 12 months of age. TCF4 hemizygosity also conferred an increased risk of early death principally due to aspiration-related complications. Hemizygosity for TCF4 confers a significant impact primarily with regard to cognitive and motor development, resulting in a very different prognosis for individuals hemizygous for TCF4 when compared to individuals hemizygous for other regions of distal 18q.
    Human Genetics 06/2011; 130(6):777-87. · 4.63 Impact Factor
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    ABSTRACT: To characterize ophthalmic findings in patients with tetrasomy 18p, a rare chromosomal anomaly that has been previously associated with strabismus. All subjects underwent a complete eye examination to screen for ocular pathology. A total of 25 subjects (13 female) were examined after they were diagnosed with tetrasomy 18p. The average age of subjects was 8.2 years (range, 13 months to 22 years). Of the 25 subjects, 18 (72% of examined subjects, 42% of the cohort) showed evidence of strabismus; 16 had esotropia (8 uncategorized, 5 infantile, and 3 accommodative), 1 had esophoria, and 1 was diagnosed with intermittent exotropia. The coincidence of esotropia with tetrasomy 18p indicates the need to routinely screen these patients for strabismus at the time of diagnosis.
    Journal of AAPOS: the official publication of the American Association for Pediatric Ophthalmology and Strabismus / American Association for Pediatric Ophthalmology and Strabismus 06/2011; 15(3):268-71. · 1.07 Impact Factor
  • Carisse M Orsi, Daniel E Hale, Jane L Lynch
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    ABSTRACT: To provide updated summary of recently published data regarding pediatric obesity epidemiology. There is a burgeoning literature of pediatric obesity epidemiology, with type 2 diabetes trends serving as the harbinger for obesity related diseases in children. The National Health and Nutrition Examination Survey and Pediatric Nutrition Surveillance System report a tripling of the prevalence of BMI at least 95% (obesity) among US school-age children and adolescents over the past three decades. Recent updates provide insight into infants and toddler obesity and explore the impact of ethnicity, socioeconomic status, school setting and geographic variations. International data confirm similar upward shifts in pediatric BMI distribution, especially in countries undergoing economic transitions favoring industrialized, western urban lifestyles. The health and financial consequences of this epidemic are a complex global public health dilemma. International efforts are underway to reverse these obesity trends. On-going analysis of obesity prevalence and exploration of potential causal associations are required to implement and assess the effectiveness of interventions and policies.
    Current opinion in endocrinology, diabetes, and obesity 02/2011; 18(1):14-22. · 3.77 Impact Factor
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    Jannine D Cody, Daniel E Hale
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    ABSTRACT: Nine out of 10 people has a chromosome copy number variation (CNV) of >1,000 bp of DNA. In some cases they are inconsequential, in other cases the variations cause disease or disability, and in most cases the relevance has not been elucidated. Several studies describe CNVs as "normal" biological variants while other studies suggest that CNVs may be associated with developmental disability. A concerted effort is needed to classify genes according to their dosage sensitivity, or to their lack of sensitivity. Over time, this effort will lead to the establishment of principles that permit the prediction of the consequence of any one genomic copy number change.
    American Journal of Medical Genetics Part A 02/2011; 155A(3):469-75. · 2.30 Impact Factor
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    ABSTRACT: The goal of this study was to identify novel candidate genes that may cause or predispose to growth hormone (GH) deficiency. DNA samples from 45 individuals with isolated GH deficiency were assessed using oligonucleotide microarray comparative genomic hybridization. Five individuals with previously unreported copy number variants were identified. Two of the five individuals were hemizygous for regions already known to cause GH deficiency (chromosomes 22q11.21 and 15q26.3). The remaining three individuals had copy number changes involving two novel chromosome regions. One individual had a homozygous deletion of a 2.2 Mb region of 13q33.1 that contains a single gene: integrin, beta-like 1 (ITGBL1). The remaining two individuals had duplications of 4.7 Mb on chromosome 20q13.13. This region includes eight genes not previously identified as copy number variants. These genes are ARFGEF2, CSE1L, DDX27, ZNFX1, C20orf199, SNORD12, KCNB1, and PTGIS. Thus, further investigations into these potential candidate genes are necessary.
    Journal of pediatric endocrinology & metabolism: JPEM 11/2010; 23(11):1159-64. · 0.75 Impact Factor
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    ABSTRACT: Thus far, the phenotype of tetrasomy 18p has been primarily delineated by published case series and reports. Findings reported in more than 25% of these cases include neonatal feeding problems, growth retardation, microcephaly, strabismus, muscle tone abnormalities, scoliosis/kyphosis, and variants on brain MRI. Developmental delays and cognitive impairment are universally present. The purpose of this study was to more fully describe tetrasomy 18p at both the genotypic and the phenotypic levels. Array CGH was performed on 43 samples from individuals with tetrasomy 18p diagnosed via routine karyotype. The medical records of 42 of these 43 individuals were reviewed. In order to gain additional phenotypic data, 31 individuals with tetrasomy 18p underwent a series of clinical evaluations at the Chromosome 18 Clinical Research Center. Results from the molecular analysis indicated that 42 of 43 samples analyzed had 4 copies of the entire p arm of chromosome 18; one individual was also trisomic for a section of proximal 18q. The results of the medical records review and clinical evaluations expand the phenotypic description of tetrasomy 18p to include neonatal jaundice and respiratory distress; recurrent otitis media; hearing loss; seizures; refractive errors; constipation and gastroesophageal reflux; cryptorchidism; heart defects; and foot anomalies. Additional findings identified in a small number of individuals include hernias, myelomeningocele, kidney defects, short stature, and failure to respond to growth hormone stimulation testing. Additionally, a profile of dysmorphic features is described. Lastly, a series of clinical evaluations to be considered for individuals with tetrasomy 18p is suggested.
    American Journal of Medical Genetics Part A 09/2010; 152A(9):2164-72. · 2.30 Impact Factor
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    ABSTRACT: Previous research has suggested that individuals with constitutional hemizygosity of 18q have a higher risk of autistic-like behaviors. We sought to identify genomic factors located on chromosome 18 as well as other loci that correlate with autistic behaviors. One hundred and five individuals with 18q- were assessed by high-resolution oligo aCGH and by parental ratings of behavior on the Gilliam Autism Rating Scale. Forty-five individuals (43%) had scores within the "possibly" or "very likely" categories of risk for an autism diagnosis. We searched for genetic determinants of autism by (1) identifying additional chromosome copy number changes (2) Identifying common regions of hemizygosity on 18q, and (3) evaluating four regions containing candidate genes located on 18q (MBD1, TCF4, NETO1, FBXO15). Three individuals with a "very likely" probability of autism had a captured 17p telomere in addition to the 18q deletion suggesting a possible synergy between hemizygosity of 18q and trigosity of 17p. In addition, two of the individuals with an 18q deletion and a "very likely" probability of autism rating had a duplication of the entire short arm of chromosome 18. Although no common region of hemizygosity on 18q was identified, analysis of four regions containing candidate genes suggested that individuals were significantly more likely to exhibit autistic-like behaviors if their region of hemizygosity included TCF4, NETO1, and FBXO15 than if they had any other combination of hemizygosity of the candidate genes. Taken together, these findings identify several new potential candidate genes or regions for autistic behaviors.
    Human Genetics 05/2010; 128(2):155-64. · 4.63 Impact Factor
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    ABSTRACT: Chromosome 18 abnormalities are associated with a range of physical abnormalities such as short stature and hearing impairments. Psychiatric manifestations have also been observed. This study focuses on the presentations of psychiatric syndromes as they relate to specific chromosomal abnormalities of chromosome 18. Twenty-five subjects (13 with an 18q deletion, 9 with 18p tetrasomy, and 3 with an 18p deletion), were interviewed by psychiatrists (blind to specific chromosomal abnormality) using the DIGS (subjects 18 and older) or KSADS-PL (subjects under 18). A consensus best estimation diagnostic process was employed to determine psychiatric syndromes. Oligonucleotide Array Comparative Genomic Hybridization (Agilent Technologies) was utilized to define specific regions of chromosome 18 that were deleted or duplicated. These data were further analyzed to determine critical regions of the chromosome as they relate to phenotypic manifestations in these subjects. 58.3% of the chromosome 18q- deletion subjects had depressive symptoms, 58.3% had anxiety symptoms, 25% had manic symptoms, and 25% had psychotic symptoms. 66.6% of the chromosome 18p- deletion subjects had anxiety symptoms, and none had depressive, manic, or psychotic symptoms. Fifty percent of the chromosome 18p tetrasomy subjects had anxiety symptoms, 12.5% had psychotic symptoms, and 12.5% had a mood disorder. All three chromosomal disorders were associated with high anxiety rates. Psychotic, manic and depressive disorders were seen mostly in 18q- subjects and this may be helpful in narrowing regions for candidate genes for these psychiatric conditions.
    American Journal of Medical Genetics Part B Neuropsychiatric Genetics 11/2009; 153B(3):837-45. · 3.23 Impact Factor
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    ABSTRACT: Microarray technology has revolutionized the field of clinical genetics with the ability to detect very small copy number changes. However, challenges remain in linking genotype with phenotype. Our goal is to enable a clinical geneticist to align the molecular karyotype information from an individual patient with the annotated genomic content, so as to provide a clinical prognosis. We have combined data regarding copy number variations, microdeletion syndromes, and classical chromosome abnormalities, with the sparse but growing knowledge about the biological role of specific genes to create a genomic map of Chromosome 18 with clinical utility. We have created a draft model of such a map, drawing from our long-standing interest in and data regarding the abnormalities of Chromosome 18. We have taken the first step toward creating a genomic map that can be used by the clinician in counseling and directing preventive or symptomatic care of individuals with Chromosome 18 abnormalities.
    Genetics in medicine: official journal of the American College of Medical Genetics 10/2009; 11(11):778-82. · 3.92 Impact Factor
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    ABSTRACT: One of our primary goals is to help families who have a child with an 18q deletion anticipate medical issues in order to optimize their child's medical care. To this end we have narrowed the critical regions for four phenotypic features and determined the penetrance for each of those phenotypes when the critical region for that feature is hemizygous. We completed molecular analysis using oligo-array CGH and clinical assessments on 151 individuals with deletions of 18q and made genotype-phenotype correlations defining or narrowing critical regions. These nested regions, all within 18q22.3 to q23, were for kidney malformations, dysmyelination of the brain, growth hormone stimulation response failure, and aural atresia. The region for dysmyelination and growth hormone stimulation response failure were identical and was narrowed to 1.62 Mb, a region containing five known genes. The region for aural atresia was 2.3 Mb and includes an additional three genes. The region for kidney malformations was 3.21 Mb and includes an additional four genes. Penetrance rates were calculated by comparing the number of individuals hemizygous for a critical region with the phenotype to those without the phenotype. The kidney malformations region was 25% penetrant, the dysmyelination region was 100% penetrant, the growth hormone stimulant response failure region was 90% penetrant with variable expressivity, and the aural atresia region was 78% penetrant. Identification of these critical regions suggest possible candidate genes, while penetrance calculations begin to create a predictive phenotypic description based on genotype.
    American Journal of Medical Genetics Part A 08/2009; 149A(7):1421-30. · 2.30 Impact Factor
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    ABSTRACT: The advent of oligonucleotide array comparative genomic hybridization (aCGH) has revolutionized diagnosis of chromosome abnormalities in the genetics clinic. This new technology also has valuable potential as a research tool to investigate larger genomic rearrangements that are typically diagnosed via routine karyotype. aCGH was used as a tool for the high-resolution analysis of chromosome content in individuals with known deletions of chromosome 18. The aim of this study was to clarify the precise location of the breakpoints as well as to determine the presence of occult translocations creating additional deletions and duplications. One hundred eighty-nine DNA samples from individuals with 18q deletions were analyzed. No breakpoint clusters were identified, as no more than two individuals had breakpoints within 2 kb of each other. Only two regions of 18q were never found to be haploid, suggesting the existence of haplolethal genes in those regions. Of the individuals with only a chromosome 18 abnormality, 17% (n = 29) had interstitial deletions. Six percent (n = 11) had a region of duplication immediately proximal to the deletion. Eight percent (n = 15) had more complex rearrangements with captured (non-18q) telomeres thus creating a trisomic region. The 15 captured telomeres originated from a limited number of other telomeres (4q, 10q, 17p, 18p, 20q, and Xq). These data were converted into a format for ease of viewing and analysis by creating custom tracks for the UCSC Genome Browser. Taken together, these findings confirm a higher level of variability and genomic complexity surrounding deletions of 18q than has previously been appreciated.
    American Journal of Medical Genetics Part A 08/2009; 149A(7):1431-7. · 2.30 Impact Factor
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    ABSTRACT: Recurrent constitutional non-Robertsonian translocations are very rare. We present the third instance of cryptic, unbalanced translocation between 4q and 18q. This individual had an apparently normal karyotype; however, after subtelomere fluorescence in situ hybridization (FISH), he was found to have a cryptic unbalanced translocation between 4q and 18q [ish der(18)t(4;18)(q35;q23)(4qtel+,18qtel-)]. Oligonucleotide array comparative genomic hybridization (aCGH) refined the breakpoints in this child and in the previously reported child and indicated that the breakpoints were within 20 kb of each other, suggesting that this translocation is, indeed, recurrent. A comparison of the clinical presentation of these individuals identified features that are characteristic of both 18q- and 4q+ as well as features that are not associated with either condition, such as a prominent metopic ridge, bitemporal narrowing, prominent, and thick eyebrows. Individuals with features suggestive of this 4q;18q translocation but a normal karyotype warrant aCGH or subtelomere studies.
    American Journal of Medical Genetics Part A 11/2008; 146A(22):2898-904. · 2.30 Impact Factor

Publication Stats

3k Citations
619.88 Total Impact Points


  • 1997–2014
    • University of Texas Health Science Center at San Antonio
      • • Department of Pediatrics
      • • Department of Cellular and Structural Biology
      • • Division of Hospital Medicine
      San Antonio, Texas, United States
  • 2013
    • University of Texas Health Science Center at Tyler
      Tyler, Texas, United States
  • 1997–2011
    • Texas Tech University Health Sciences Center
      • Department of Pediatrics
      Lubbock, TX, United States
  • 2008
    • University of Pittsburgh
      • Department of Pathology
      Pittsburgh, PA, United States
  • 2005
    • University of Texas at Austin
      • Department of Educational Psychology
      Texas City, TX, United States
  • 1984–1998
    • The Children's Hospital of Philadelphia
      • • Department of Pediatrics
      • • Division of Endocrinology and Diabetes
      Philadelphia, Pennsylvania, United States
  • 1996
    • University of Texas at San Antonio
      San Antonio, Texas, United States
  • 1986–1996
    • University of Washington Seattle
      • • Department of Obstetrics and Gynecology
      • • Department of Pediatrics
      Seattle, WA, United States
    • University of Pennsylvania
      • Department of Pediatrics
      Philadelphia, Pennsylvania, United States
  • 1995
    • University of Texas Southwestern Medical Center
      • Department of Pathology
      Dallas, TX, United States
    • Brown University
      • Department of Chemistry
      Providence, RI, United States
  • 1993–1995
    • Hospital of the University of Pennsylvania
      • Department of Pediatrics
      Philadelphia, Pennsylvania, United States
  • 1992
    • Baylor Health Care System
      Dallas, Texas, United States
    • Washington University in St. Louis
      • Department of Pediatrics
      San Luis, Missouri, United States
    • Yale-New Haven Hospital
      • Department of Diabetes and Endocrinology
      New Haven, Connecticut, United States
  • 1988–1992
    • Yale University
      • Department of Genetics
      New Haven, CT, United States
    • University of Massachusetts Medical School
      Worcester, Massachusetts, United States
    • Hartford Hospital
      • Department of Pediatrics
      Hartford, Connecticut, United States
  • 1991
    • Ospedale Pediatrico Bambino Gesù
      Roma, Latium, Italy
  • 1987
    • Riley Hospital for Children
      Indianapolis, Indiana, United States