H E Wyandt

Boston University, Boston, MA, United States

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Publications (47)146.25 Total impact

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    ABSTRACT: A 10-year-old African-American male has been followed since 2 years of age due to his mental retardation, severe behavioral problems, and dysmorphism. Conventional cytogenetic analysis, chromosome painting, high-resolution comparative genomic hybridization (HR-CGH), and bacterial artificial chromosome fluorescent in situ hybridization (BAC FISH) revealed an apparent duplication in the short arm of a chromosome 11, dup(11)(p14.3p15.1), seen also in his mentally retarded mother. The proband had moderate to severe mental retardation, a history of IUGR, infantile hypotonia, FTT, exotropia, inguinal hernia repair, and several dysmorphic features. His mother had mild mental retardation, a history of impulsivity, assaultive outbursts, and similar dysmorphism. Although G-banding and FISH indicated a duplication, HR-CGH confined the localization of material to bands 11p14-11p15 and aided the selection of locus-specific BAC clones to more precisely characterize the duplicated region. To our knowledge, the results represent the first example of a familial, cytogenetically visible duplication of euchromatin in 11p that excludes the Beckwith-Wiedemann syndrome critical region. It is possible that one or more genes had been disrupted at the breakpoints of the above structural chromosomal rearrangement giving rise to the present phenotype.
    Experimental and Molecular Pathology 07/2006; 80(3):262-6. · 2.13 Impact Factor
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    ABSTRACT: A newborn female presented with costovertebral dysplasia (CVD), subtle facial anomalies, and neonatal respiratory distress. Her karyotype demonstrated a small supernumerary NOR-positive marker that was subsequently identified as del(22)(q11.2). This extra structurally abnormal chromosome was found by DNA microsatellite marker analyses to be derived from a paternal chromosome 22. The child has had severe growth and developmental delay along with pulmonary insufficiency and hypoxia but is presently stable at age 20 months. Findings in our patient correlate with similar observations in children with small markers derived from D/G and D/D translocations reported before banding technology was available. These reports and recent mapping results suggest that a pericentric gene family, distributed on one or more acrocentric chromosomes, may have played a role in the development of the human axial skeleton. Data from additional studies will be needed to confirm or refute this hypothesis.
    Experimental and Molecular Pathology 05/2006; 80(2):197-200. · 2.13 Impact Factor
  • Herman E. Wyandt, Vijay S. Tonk, Xinli Huang
    Fetal Diagnosis and Therapy 01/2006; · 1.90 Impact Factor
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    ABSTRACT: Rapid fluorescence in situ hybridization (FISH) performed on 1,788 amniocenteses, using Aneuvision (Vysis) probes for chromosomes 13, 18, 21, X, and Y, over several years, yielded 115 cases with percentages of aneuploidy between 4 and 100%. All cases above 60% were confirmed to be positive by chromosome analysis. Fifteen of forty-one cases that would be considered inconclusive by generally accepted criteria (i.e. with less than 60% of cells with an abnormal signal pattern) revealed lower cutoffs to be positive when confirmed by chromosome analysis. For trisomy 21, 6 cases with percentages from 36 to 57% were positive; 4 of 7 cases with percentages from 22.5 to 33% were positive; 11 cases with percentages of 13% or less were negative. Similar trends were found for aneuploidies of 13, 18, X, and Y. However, the number of abnormal cases is still too small to determine definitive cutoffs in the <60% gray zone. An average of 57 metaphases was analyzed for cases with FISH percentages below 60%. Despite the wide range of abnormal FISH percentages for chromosomally positive cases, we found no examples of autosomal mosaicism in this series. Although sex chromosome mosaicism was cytogenetically evident in several cases, there was little direct correlation between cytogenetic and rapid FISH results. FISH results involving sex chromosomes were more frequently confounded by maternal cell contamination and other technical factors.
    Fetal Diagnosis and Therapy 01/2006; 21(2):235-40. · 1.90 Impact Factor
  • Experimental and Molecular Pathology 01/2006; · 2.13 Impact Factor
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    ABSTRACT: We report on a female patient with severe-profound mental retardation, multiple congenital anomalies, as well as a history of mosaicism for partial 1q trisomy in the amniotic fluid and a previous Wilms tumor specimen. Peripheral blood and fibroblasts were studied and did not demonstrate the mosaicism initially detected for 1q. Array comparative genomic hybridization yielded negative results. Additional cytogenetic studies helped clarify the previous findings and revealed evidence of partial 1q trisomy mosaicism in normal kidney tissue and in a kidney lesion. GTG-banded results showing low-percentage mosaicism for the structural rearrangement der(1)t(1;1)(p36.1;q23) in both tissues were corroborated by fluorescence in situ hybridization studies. We hypothesize that the partial 1q trisomy predisposed the target tissue (in this case kidney) to neoplasia. This study provides further support for the hypothesis that certain constitutional chromosomal abnormalities can predispose to cancer. As detection of a low-percentage mosaicism may be hampered by the limits imposed by currently available technology and the constraint of a finite sample size, extra vigilance in monitoring other somatic tissues will be needed throughout the patient's lifetime. Anticipatory clinical guidance and prognostication are meaningful only if given accurate cytogenetic diagnoses. To the best of our knowledge, this is the first reported case of Wilms tumor associated with constitutional partial 1q trisomy, either in pure or mosaic form, with the particular 1q23 breakpoint in conjunction with a break on 1p36.1.
    Cancer Genetics and Cytogenetics 11/2005; 162(2):166-71. · 1.93 Impact Factor
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    ABSTRACT: We describe the structure of a supernumerary marker in a child who presented with a right atretic ear and multiple congenital anomalies. Using G-banding, fluorescent in situ hybridization (FISH), P1 artificial chromosome FISH and high-resolution comparative genomic hybridization (CGH), the marker was demonstrated to be a derivative chromosome resulting from malsegregation of a paternal 8;22 translocation: 47,XY, +der(22)t(8;22)(q24.1; q11.2). This case is noteworthy because the marker, while sharing similarities to der(22) in the Cat Eye syndrome (CES), also contains chromosome 8q material. This partial 8q trisomy confounds the diagnosis of CES associated with pure trisomy or pure tetrasomy 22q. The paternal translocation is noted with prolonged infertility and oligospermia, which again highlights the utility and necessity of chromosome analysis in this setting.
    Clinical Genetics 09/2005; 68(2):146-51. · 3.94 Impact Factor
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    ABSTRACT: At 6 years of age, a boy with bilateral sensorineural deafness, lateral displacement of inner canthi, a bulbous nasal tip, synophrys, and cryptorchidism was clinically diagnosed as having Waardenburg's syndrome type I (WS-1). In addition, he had a lumbar spina bifida with hydrocephalus shunted on the second day of life and severe mental retardation with a head circumference at the fifth percentile. Neither parent showed signs of WS-1, and the family history was negative. Because of the WS-1 features, attention was focused on the PAX3 location in 2q, at which time a de novo paracentric inversion of 2q23-q37.1 was noted. Subsequent high-resolution chromosome analysis 8 years later indicated a complex rearrangement involving regions 2q31-q35 and 2q13-q21. Whole chromosome painting and high-resolution comparative genomic hybridization yielded negative results for any translocation, duplication, or deletion of any chromosome segments. Sequencing of the PAX3 gene yielded no detectable mutation. Fluorescent in situ hybridization (FISH) studies with human BAC clones revealed five breakpoints in chromosome 2q resulting in two paracentric inversions and one insertion, the karyotype being interpreted as 46,XY,der(2)inv(2)(q13q21)inv(2)(q21q24.2)ins(2)(q24.2q33q35). In this extremely rare chromosomal rearrangement, the FISH result showed a breakpoint at 2q35 being proximal to and without involvement of the PAX3 gene. While further studies continue, possible interpretations include involvement of a regulatory gene(s) for PAX 3 and other genes at the other breakpoints related causally to the spina bifida and mental retardation.
    Clinical Genetics 08/2004; 66(1):46-52. · 3.94 Impact Factor
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    ABSTRACT: We present our experience with cross-hybridization of D15Z1, used in combination with D15S10, D15S11 or SNRPN, in 109 clinical cases referred for Angelman syndrome (AS), Prader-Willi syndrome (PWS), for autism to rule out duplication of 15q11.2, or to identify structural chromosome abnormalities thought to involve chromosome 15. Nine cases with normal karyotypes studied with at least one of these probe mixtures showed an extra signal with D15Z1 on a chromosome 14. One case showed absence of the D15Z1 signal from 15p and one case showed an extra signal with D15Z1 on both chromosome 14s. Sixteen cases from this series had structural abnormalities, which included ten cases with supernumerary markers, three of which had a D15Z1 signal on a chromosome 14. The remaining cases did not have an extra signal on chromosome 14, but included rearrangements between Y and 15, 15 and 19, and a r(15), all with breakpoints in 15p11.1 or p11.2. Of the three cases with a supernumerary marker and an extra D15Z1 signal on a chromosome 14, one was a maternally derived marker, while the variant 14 was paternal in origin. The other two markers were de novo. The high frequency of variant 14 in cases with supernumerary markers (30%) was not significant by Chi-square analysis compared to the overall frequency in 109 cases of 11.9%. The overall frequency is consistent with a previous report by Stergianou et al. (1993). We can now add that a false-negative result may occur slightly less than 1% of the time. The chance that both chromosome 14 homologs will be positive for D15Z1 is theoretically about 1 in 300. If associated with an abnormal phenotype, the possibility of uniparental disomy should be ruled out.
    Journal of the Association of Genetic Technologists 02/2003; 29(4):146-151.
  • X-L.Huang, HE.Wyandt, JM. Milunsky
    Am J Hum Genet. 01/2003;
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    ABSTRACT: Disease associated balanced chromosome rearrangements (DBCR) causing truncation, deletion, inactivation or over-expression of specific genes are instrumental in identifying and cloning several disease genes and are estimated to be much more common than anticipated. In one survey, the minimal frequency of combined balanced de novo reciprocal translocations and inversions causing abnormal phenotype is estimated to be 0.17%, a sixfold increase compared to the general population suggesting a causative linkage between the abnormality and the observed phenotypic traits. Here, we report two new cases of apparently balanced de novo translocations resulting in developmental delay and dysmorphic features.
    Annales de Génétique 01/2003; 46(1):37-43.
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    ABSTRACT: Karyotypes from independent amniocenteses reflected a rare, unstable, functionally dicentric Robertsonian translocation chromosome in most cells in male Twin B who grew more slowly than the chromosomally normal female sib (Twin A). Twin B's balanced de novo Robertsonian translocation dic(13;14)(p11.1;p11.1), present in 81% of cells, underwent recurrent centromeric fission in 6 out of 30 independent colonies that explains a balanced 46,XY,-13,+fis(13)(p11.1),-14,+fis(14)(p11.1) karyotype. Aneuploidy for chromosomes 13q or 14q was present in 5% of cells. Instability of the Robertsonian translocation was evident because nine of the 30 colonies (30%) grown from single amniocytes had metaphase cells with more than one chromosome complement. Although uniparental disomy was excluded and a targeted ultrasound was normal, the couple was advised of the uncertain but real risk of abnormalities in Twin B and the risk to Twin A of terminating Twin B. The pregnancy proceeded and at 31 weeks gestation Twin A was in the 33rd percentile for size and Twin B in the 1st percentile. At 32 weeks, chromosome analysis revealed a balanced 45,XY,dic(13;14)(p11.1;p11.1) karyotype in all of Twin B's newborn cord blood cells with no evidence of fission or aneuploidy. Selection against unbalanced mitotic products of the unstable, functionally dicentric chromosome in early fetal development is proposed to result in Twin B's highly discordant small birth size.
    Clinical Genetics 12/2002; 62(5):383-9. · 3.94 Impact Factor
  • D Chinnappan, A Philip, X Wu, A Pan, H E Wyandt
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    ABSTRACT: Robertsonian translocations were observed in two leukemia patients. The first case was a patient with chronic lymphocytic leukemia, who was found to have a rare Robertsonian translocation der(14;15)(q10;q10). The second case, a patient with acute myeloid leukemia, had multiple Robertsonian translocations: der(15)t(13;15)(q11.1;p11.1), der(14;22)(q10;q10), and dic(21;22)(p11.1;p11.1). Acquired multiple Robertsonian translocations have not been reported previously in leukemia.
    Cancer Genetics and Cytogenetics 01/2002; 131(2):104-8. · 1.93 Impact Factor
  • H E Wyandt
    American Journal of Medical Genetics 05/2001; 100(1):82-3.
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    ABSTRACT: A 19-week stillborn female fetus with bilateral cleft palate, horseshoe kidney, bicornuate uterus, low-set ears, and intrauterine growth retardation (IUGR) was found to have a supernumerary derivative chromosome 9 (der(9)) with an apparent tandem duplication in the long arm. PCR analysis at five polymorphic loci confirmed the duplication and showed an adjacent deletion, while whole chromosome FISH demonstrated only chromosome 9 to be involved. Further FISH studies of der(9) found the 9qh region to be duplicated, telomeric sequences to be intact, and subtelomeric sequences to be absent. Thus, the fetus was determined to be trisomic for 9pter-->9q12 and 9q34.3-->9qter, tetrasomic for 9q12--> 9q33, and disomic for 9q33-->9q34.3. These results are consistent with a tandem duplication of 9q12-->9q33 and adjacent distal deletion as designated by the karyotype, 47,XX,+der(9)dup(9) (q12q33)del(9) (q33q34.3).ish der(9)(WCP9+,D9Z1x2,STP9q-, AHT+) de novo. In addition to characterizing der(9), the combined PCR and cytogenetic studies refined the Genome Database Map of three loci (D9S907, D9S155, and D9S302) approximately to the distal 9q33 region. Without the attempt to refine breakpoints by PCR analysis, the deletion in distal 9q would not have been detected. Tandem direct duplication/deletion chromosomes have been reported in fewer cases than inverted duplication/deletions. We propose mechanisms of origin, consistent with those for recurrent inter stitial microdeletion and microduplication syndromes, shown to arise by recombination at homologous, flanking DNA sequences.
    American Journal of Medical Genetics 08/2000; 93(4):305-12.
  • Annals of the New York Academy of Sciences 10/1999; 883:472-6. · 4.38 Impact Factor
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    ABSTRACT: An amniocyte culture was found to be mosaic for 45,X/46,X, idic(X)(p11.2)/ 47,X, idic(X)(p11.2),idic(X)(p11.2) cell lines, reflecting mitotic nondisjunction of the idic(X)(p11.2) chromosome. Upon learning of abnormal karyotype and ultrasound findings, the parents decided to discontinue the pregnancy. Subsequent cultures of fetal skin, kidney, and lung were mosaic 45,X/46,X,idic(X)(p11.2) reflecting mitotic loss of the unstable idic(X)(p11.2) chromosome. C-banding and in situ hybridization of X chromosome-specific alpha-satellite probe to metaphase fetal cells confirmed two centromeres on the idic(X)(p11.2) chromosome with both centromeres appearing to be active in two-thirds of cells. This result was confirmed by centromere protein-E (CENP-E) antibody staining which delineated 80% of scored cells with two active centromeres and 20% with 1 active centromere. Bromodeoxyuridine (BrdU) incorporation and acridine orange staining characterized the DNA replication pattern of the idic(X)(p11.2) chromosome as late and symmetrically replicating. Polymerase chain reaction analysis of highly polymorphic loci determined that the normal X chromosome carried paternal alleles and the idic(X)(p11.2) chromosome carried maternal alleles from only one grandparental chromosome. Overall, the results suggest that recombination occurred between two maternal sister chromatids both in the same chromosome band Xp11.2 (isolocal) prior to maternal meiosis II anaphase to generate an unstable maternal idic(X)(p11.2) chromosome. Additional factors that could contribute to i(Xq) and idic(X) formation and instability are discussed along with a mechanism to explain the high frequency of intrauterine loss in 45,X pregnancies.
    American Journal of Medical Genetics 09/1999; 85(5):429-37.
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    ABSTRACT: Multiple genetic loci have been implicated in the search for schizophrenia susceptibility genes, none having been proven as causal. Genetic heterogeneity is probable in the polygenic etiology of schizophrenia. We report on two unrelated Caucasian women with paranoid schizophrenia (meeting Diagnostic and Statistical Manual of Mental Disorders (DSM IV) criteria) who have an Xp22.3 overlapping deletion characterized by fluorescence in situ hybridization (FISH). Patient 1 was previously reported by us (Wyandt HE, Bugeau-Michaud L, Skare JC, Milunsky A. Partial duplication of Xp: a case report and review of previously reported cases. Amer J Med Genet 1991: 40: 280-283) to have a de novo partial duplication of Xp. At that time, she was a 24-year-old woman with short stature, irregular menses, other abnormalities suggestive of Turner syndrome, and paranoid schizophrenia. Recently, FISH analysis demonstrated that she has an inverted duplication (X)(p22.1p11.2) and a microscopic deletion (X)(p22.2p22.3) between DXS1233 and DXS7108 spanning approximately 16-18 cM. Patient 2 is a 14-year-old girl with short stature, learning disabilities, and paranoid schizophrenia. High-resolution chromosome analysis revealed a de novo deletion involving Xp22. FISH analysis showed that the deletion (X)(p22.2p22.3) spanned 10-12 cM between AFMB290XG5 and DXS1060. Given that deletions of Xp22 are not common events, the occurrence of two unrelated schizophrenia patients with an overlapping deletion of this region would be extraordinarily rare. Hence, the deletion within Xp22.3 almost certainly contains a gene involved in the pathogenesis of paranoid schizophrenia.
    Clinical Genetics 07/1999; 55(6):455-60. · 3.94 Impact Factor
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    ABSTRACT: To evaluate the assumptions on which the American College of Medical Genetics (ACMG) Standards and Guidelines for detecting mosaicism in amniotic fluid cultures are based. Data from 653 cases of amniotic fluid mosaicism were collected from 26 laboratories. A chi-square goodness-of-fit test was used to compare the observed number of mosaic cases with the expected number based on binomial distribution theory. Comparison of observed data from the in situ colony cases with the expected distribution of cases detected based on the binomial distribution did not reveal a significant difference (P = 0.525). The empirical data fit the binomial distribution. Therefore, binomial theory can be used as an initial discussion point for determining whether ACMG Standards and Guidelines are adequate for detecting mosaicism.
    Genetics in Medicine 02/1999; 1(3):94-7. · 5.56 Impact Factor
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    ABSTRACT: We describe a liveborn infant with uniparental disomy (UPD) with trisomy 15 mosaicism. Third trimester amniocentesis yielded a 46,XX/47,XX,+15 karyotype. Symmetrical growth retardation, distinct craniofacies, congenital heart disease, severe hypotonia and minor skeletal anomalies were noted. The infant died at 6 weeks of life. Peripheral lymphocyte chromosomes were “normal” 46,XX in 100 cells. Parental lymphocyte chromosomes were normal. Skin biopsy showed 47,XX,+15 in 80% of fibroblasts and results were equivalent in fibroblasts from autopsy lung tissue. Molecular analysis revealed maternal uniparental heterodisomy for chromosome 15 in the 46,XX cell line. We describe an emerging phenotype of trisomy 15 mosaicism, confirm that more than one tissue should be studied in all cases of suspected mosaicism, and suggest that UPD be considered in all such cases. © 1996 Wiley-Liss, Inc.
    American Journal of Medical Genetics 12/1998; 61(3):269 - 273.

Publication Stats

430 Citations
146.25 Total Impact Points


  • 1991–2006
    • Boston University
      • Center for Human Genetics
      Boston, MA, United States
  • 1989–2004
    • Beverly Hospital, Boston MA
      Beverly, Massachusetts, United States
  • 1989–2001
    • University of Massachusetts Boston
      Boston, Massachusetts, United States
  • 1993
    • Boston Medical Center
      Boston, Massachusetts, United States
  • 1989–1993
    • University of Massachusetts Medical School
      Worcester, Massachusetts, United States
  • 1990
    • Tufts Medical Center
      Boston, Massachusetts, United States
    • Center for Human Genetics, Inc.
      Cambridge, Massachusetts, United States