Wladimir Wertelecki

University of South Alabama, Mobile, Alabama, United States

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Publications (67)284.33 Total impact

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    ABSTRACT: Published prevalence rates of congenital diaphragmatic hernia (CDH) vary. This study aims to describe the epidemiology of CDH using data from high-quality, population-based registers belonging to the European Surveillance of Congenital Anomalies (EUROCAT). Cases of CDH delivered between 1980 and 2009 notified to 31 EUROCAT registers formed the population-based case series. Prevalence over time was estimated using multilevel Poisson regression, and heterogeneity between registers was evaluated from the random component of the intercept. There were 3373 CDH cases reported among 12 155 491 registered births. Of 3131 singleton cases, 353 (10.4%) were associated with a chromosomal anomaly, genetic syndrome or microdeletion, 784 (28.2%) were associated with other major structural anomalies. The male to female ratio of CDH cases overall was 1:0.69. Total prevalence was 2.3 (95% CI 2.2 to 2.4) per 10 000 births and 1.6 (95% CI 1.6 to 1.7) for isolated CDH cases. There was a small but significant increase (relative risk (per year)=1.01, 95% credible interval 1.00-1.01; p=0.030) in the prevalence of total CDH over time but there was no significant increase for isolated cases (ie, CDH cases that did not occur with any other congenital anomaly). There was significant variation in total and isolated CDH prevalence between registers. The proportion of cases that survived to 1 week was 69.3% (1392 cases) for total CDH cases and 72.7% (1107) for isolated cases. This large population-based study found an increase in total CDH prevalence over time. CDH prevalence also varied significantly according to geographical location. No significant association was found with maternal age. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
    Archives of Disease in Childhood - Fetal and Neonatal Edition 11/2014; DOI:10.1136/archdischild-2014-306174 · 3.86 Impact Factor
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    ABSTRACT: Fetal alcohol spectrum disorders are thought to be a leading cause of developmental disabilities worldwide. However, data are lacking on alcohol use among pregnant women in many countries. The purpose of this study was to evaluate the prevalence and predictors of alcohol consumption by pregnant women in Ukraine. Cross-sectional screening of pregnant women was conducted in 2 regions of Ukraine during the recruitment phase of an ongoing clinical study that is part of the Collaborative Initiative on Fetal Alcohol Spectrum Disorders. Women attending a routine prenatal visit at 1 of 2 participating regional centers were asked about alcohol consumption. Quantity and frequency of alcoholic beverages consumed in the month around conception and in the most recent month of pregnancy were measured using a standard interview instrument. Between 2007 and 2012, 11,909 pregnant women were screened on average in the second trimester of pregnancy. Of these, 92.7% reported being ever-drinkers. Among ever-drinkers, 54.8% reported drinking alcohol in the month around conception and 12.9% consumed at least 3 drinks on at least 1 day in that time period. In the most recent month of pregnancy, 46.3% continued to report alcohol use and 9.2% consumed at least 3 drinks per day. Significant predictors of average number of drinks or heavier drinking per day in either time period in pregnancy included lower gravidity, being single, unmarried/living with a partner, or separated, lower maternal education, smoking, younger age at initiation of drinking, and higher score on the TWEAK screening test for harmful drinking. These findings support the need for education/intervention in women of childbearing age in Ukraine and can help inform targeted interventions for women at risk of an alcohol-exposed pregnancy. The initiation of a standard screening protocol in pregnancy is a step in the right direction.
    Alcoholism Clinical and Experimental Research 04/2014; 38(4):1012-9. DOI:10.1111/acer.12318 · 3.31 Impact Factor
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    ABSTRACT: This population-based descriptive epidemiology study demonstrates that rates of conjoined twins, teratomas, neural tube defects, microcephaly, and microphthalmia in the Rivne province of Ukraine are among the highest in Europe. The province is 200 km distant from the Chornobyl site and its northern half, a region known as Polissia, is significantly polluted by ionizing radiation. The rates of neural tube defects, microcephaly and microphthalmia in Polissia are statistically significantly higher than in the rest of the province. A survey of at-birth head size showed that values were statistically smaller in males and females born in one Polissia county than among neonates born in the capital city. These observations provide clues for confirmatory and cause-effect prospective investigations. The strength of this study stems from a reliance on international standards prevalent in Europe and a decade-long population-based surveillance of congenital malformations in two distinct large populations. The limitations of this study, as those of other descriptive epidemiology investigations, is that identified cause-effect associations require further assessment by specific prospective investigations designed to address specific teratogenic factors.
    Congenital Anomalies 01/2014; 54(3). DOI:10.1111/cga.12051 · 0.78 Impact Factor
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    B. Wang, W. Wertelecki
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    ABSTRACT: Rounding of data is common in practice. The problem of estimating the underlying density function based on data with rounding errors is addressed. A parametric maximum likelihood estimator and a nonparametric bootstrap kernel density estimator are proposed. Simulations indicate that the maximum likelihood approach performs well when prior information on the functional form of the underlying distribution is available, while the kernel-type estimator attains stable and good performance in various cases. The proposed methods are further applied to detect the distributional difference of head circumferences from two Chernobyl impacted regions of Ukraine.
    Computational Statistics & Data Analysis 09/2013; 65:4–12. DOI:10.1016/j.csda.2012.02.016 · 1.15 Impact Factor
  • Alcohol and Alcoholism 08/2013; 48(suppl 1):i21-i22. DOI:10.1093/alcalc/agt092 · 2.09 Impact Factor
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    ABSTRACT: Maternal alcohol consumption during pregnancy and fetal alcohol spectrum disorders (FASDs) represent a significant public health problem. The influence of the male partner's alcohol consumption patterns and the quality of the partner's intimate relationship might be important factors to consider in the design of successful FASD prevention programs. As part of the Collaborative Initiative on Fetal Alcohol Spectrum Disorders, 166 pregnant women in two regions in Ukraine participated in an in-person interview at an average gestational age of 18-19 weeks. Subjects were classified cross-sectionally as abstainers/light drinkers (n = 80), defined as low or no consumption of alcohol in the periconceptional period and none in the most recent 2 weeks of pregnancy; discontinuers (n = 43), defined as moderate to heavy alcohol use in the periconceptional period but none during the most recent 2 weeks of pregnancy; or continuing drinkers (n = 43), defined as continued moderate to heavy alcohol use within the most recent 2 weeks of pregnancy. Women also reported on their partner's drinking behavior and on the quality of their intimate relationship. Heavy paternal drinking was significantly associated with both continuing maternal drinking in the most recent 2 weeks (adjusted odds ratio [OR] = 34.1; 95% CI [5.9, 195.8]) and being a risky drinker only around conception (adjusted OR = 27.0; 95% CI [5.0, 147.7]). In addition, women who consumed alcohol during pregnancy had lower mean scores for satisfaction with partners' relationship and ability to discuss problems (p < .05) compared with light drinkers/abstainers. This study suggests that development of partner-based interventions, as opposed to those solely focused on maternal drinking, might be warranted as a strategy to prevent FASD.
    Journal of studies on alcohol and drugs 07/2011; 72(4):536-44. DOI:10.15288/jsad.2011.72.536 · 2.27 Impact Factor
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    ABSTRACT: EUROCAT is a network of population-based congenital anomaly registries providing standardized epidemiologic information on congenital anomalies in Europe. There are three types of EUROCAT membership: full, associate, or affiliate. Full member registries send individual records of all congenital anomalies covered by their region. Associate members transmit aggregate case counts for each EUROCAT anomaly subgroup by year and by type of birth. This article describes the organization and activities of each of the current 29 full member and 6 associate member registries of EUROCAT. Each registry description provides information on the history and funding of the registry, population coverage including any changes in coverage over time, sources for ascertaining cases of congenital anomalies, and upper age limit for registering cases of congenital anomalies. It also details the legal requirements relating to termination of pregnancy for fetal anomalies, the definition of stillbirths and fetal deaths, and the prenatal screening policy within the registry. Information on availability of exposure information and denominators is provided. The registry description describes how each registry conforms to the laws and guidelines regarding ethics, consent, and confidentiality issues within their own jurisdiction. Finally, information on electronic and web-based data capture, recent registry activities, and publications relating to congenital anomalies, along with the contact details of the registry leader, are provided. The registry description gives a detailed account of the organizational and operational aspects of each registry and is an invaluable resource that aids interpretation and evaluation of registry prevalence data.
    Birth Defects Research Part A Clinical and Molecular Teratology 03/2011; 91 Suppl 1:S51-S100. DOI:10.1002/bdra.20775 · 2.21 Impact Factor
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    ABSTRACT: The health effects of chronic low-dose radiation exposure remains a controversial question. Monitoring after the Chernobyl nuclear accident in Ukraine suggested that chronic low-dose radiation exposure was not linked to cancer mortality among the general population. However, elevated rates of birth defects in contaminated compared to uncontaminated regions suggest that exposure to radiation in utero might impact development and that chronic radiation exposure might represent an underestimated risk to human health. We sought to determine current radiation exposure routes in Rivne-Polissia, a region of Ukraine contaminated by the Chernobyl accident. This represents a first step toward comprehensive studies of the effects of chronic radiation exposure on human health. We designed and administered a dietary and activity survey to 344 women in Polissia. We assessed types and sources of food consumed, types of outdoor activities, and alcohol intake. Alcohol intake was low and alone does not account for the observed high rates of birth defects. Wild foods, especially mushrooms and berries, and locally produced foods, especially milk related, were major radiation exposure routes. Additionally, women were exposed to radiation through inhalation while burning grasses and potato vines in fields, and wood for cooking and heating. Twenty four years after the Chernobyl accident, women continue to be chronically exposed to low-dose radiation at levels exceeding current recommendations. This might contribute (especially synergistically with alcohol consumption and micronutrient deficiencies) to higher prevalence of birth defects in areas of Ukraine with high levels of radiation contamination compared to uncontaminated areas.
    American Journal of Human Biology 09/2010; 22(5):667-74. DOI:10.1002/ajhb.21063 · 1.93 Impact Factor
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    ABSTRACT: Rates of Down syndrome (DS) show considerable international variation, but a systematic assessment of this variation is lacking. The goal of this study was to develop and test a method to assess the validity of DS rates in surveillance programs, as an indicator of quality of ascertainment. The proposed method compares the observed number of cases with DS (livebirths plus elective pregnancy terminations, adjusted for spontaneous fetal losses that would have occurred if the pregnancy had been allowed to continue) in each single year of maternal age, with the expected number of cases based on the best-published data on rates by year of maternal age. To test this method we used data from birth years 2000 to 2005 from 32 surveillance programs of the International Clearinghouse for Birth Defects Surveillance and Research. We computed the adjusted observed versus expected ratio (aOE) of DS birth prevalence among women 25-44 years old. The aOE ratio was close to unity in 13 programs (the 95% confidence interval included 1), above 1 in 2 programs and below 1 in 18 programs (P < 0.05). These findings suggest that DS rates internationally can be evaluated simply and systematically, and underscores how adjusting for spontaneous fetal loss is crucial and feasible. The aOE ratio can help better interpret and compare the reported rates, measure the degree of under- or over-registration, and promote quality improvement in surveillance programs that will ultimately provide better data for research, service planning, and public health programs.
    American Journal of Medical Genetics Part A 07/2010; 152A(7):1670-80. DOI:10.1002/ajmg.a.33493 · 2.05 Impact Factor
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    Wladimir Wertelecki
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    ABSTRACT: One of the populations most exposed to chronic low-dose radiation from Chornobyl (Chernobyl in Russian) lives in Polissia, the region representing the northern half of Rivne Province (Oblast) in Ukraine. Here the patterns and population rates of malformations are reported and possible etiologic factors and regional contrasts are explored. Malformations, as defined by international standards, noted among all 96 438 births in Rivne between 2000 and 2006, were analyzed statistically. Contrasts of rates in Polissia compared with the rest of Rivne also were investigated. The overall rate of neural tube defects in Rivne is among the highest in Europe (22.2 per 10,000 live births). The rates of conjoined twins and teratomas also seem to be elevated. In Polissia, the overall rates of neural tube defects are even higher (27.0 vs 18.3, respectively; odds ratio: 1.46 [95% confidence interval: 1.13-1.93]), and the rates of microcephaly and microphthalmia may also be elevated. The malformation patterns observed suggest early disruptions of blastogenesis, manifesting as alterations of body axes, twinning, duplications, laterality, and midline formation. The results are sufficiently compelling to justify continuing and expanding this investigation of malformations in chronic low-dose radiation-impacted regions of Ukraine.
    PEDIATRICS 03/2010; 125(4):e836-43. DOI:10.1542/peds.2009-2219 · 5.30 Impact Factor
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    ABSTRACT: There is increasing evidence that human pregnancy outcome can be significantly compromised by suboptimal maternal nutritional status. Poor diet results in a maternal-fetal environment in which the teratogenicity of other insults such as alcohol might be amplified. As an example, there is evidence that zinc (Zn) can interact with maternal alcohol exposure to influence the risk for fetal alcohol spectrum disorders (FASD). Studies with experimental animals have shown that the teratogenicity of alcohol is increased under conditions of Zn deficiency, whereas its teratogenicity is lessened when animals are given Zn-supplemented diets or Zn injections before the alcohol exposure. Alcohol can precipitate an acute-phase response, resulting in a subsequent increase in maternal liver metallothionein, which can sequester Zn and lead to decreased Zn transfer to the fetus. Importantly, the teratogenicity of acute alcohol exposure is reduced in metallothionein knockout mice, which can have improved Zn transfer to the conceptus relative to wild-type mice. Consistent with the above, Zn status has been reported to be low in alcoholic women at delivery. Preliminary data from two basic science and clinical nutritional studies that are ongoing as part of the international Collaborative Initiative on Fetal Alcohol Spectrum Disorders support the potential role of Zn, among other nutritional factors, relative to risk for FASD. Importantly, the nutrient levels being examined in these studies are relevant to general clinical populations and represent suboptimal levels rather than severe deficiencies. These data suggest that moderate deficiencies in single nutrients can act as permissive factors for FASD, and that adequate nutritional status or intervention through supplementation may provide protection from some of the adverse effects of prenatal alcohol exposure.
    BioFactors 03/2010; 36(2):125-35. DOI:10.1002/biof.89 · 3.00 Impact Factor
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    ABSTRACT: The aim of this pilot study was to explore possible ultrasound parameters for the early detection of alcohol-mediated fetal somatic and central nervous system (CNS) maldevelopment. Maternal alcohol ingestion during pregnancy may lead to fetal alcohol spectrum disorders (FASD), which encompass a broad range of structural abnormalities including growth impairment, specific craniofacial features and CNS abnormalities. Early detection of fetuses at risk of FASD would support earlier interventions. We performed a longitudinal prospective pilot study from 2004 to 2006 at two sites in Ukraine. A sample of pregnant women who reported consuming moderate-to-heavy amounts of alcohol participated in a comprehensive maternal interview, and received ultrasound evaluation of fetal growth and specific fetal brain measurements during the second and third trimesters. These measurements were compared with those collected from a group of pregnant women who consumed little-to-no alcohol during pregnancy, and who were recruited and followed in the same manner. From 6745 screened women, 84 moderate-to-heavy alcohol users and 82 comparison women were identified and ultrasound examinations performed. After controlling for maternal smoking, alcohol-exposed fetuses had shorter mean femur length, caval-calvarial distance and frontothalamic measurements in the second trimester (P < 0.05), and alcohol-exposed fetuses also had shorter frontothalamic distance measurements in the third trimester relative to comparison fetuses (P < 0.05). In addition, after controlling for maternal smoking, both mean orbital diameter and biparietal diameter measurements were significantly smaller on average in the alcohol-exposed group in the third trimester relative to comparison fetuses (P < 0.05). Significant differences in selected somatic and brain measurements were noted between alcohol-exposed and comparison fetuses, suggesting these markers may be further explored for clinical utility in prenatal identification of affected children. Further study correlating these findings with alcohol-related physical features of the newborn and subsequent comparisons of neuro-developmental outcomes will help define potential uses of prenatal ultrasound for intervention and prevention of FASD.
    Ultrasound in Obstetrics and Gynecology 06/2009; 33(6):683-9. DOI:10.1002/uog.6379 · 3.14 Impact Factor
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    Ultrasound in Obstetrics and Gynecology 10/2007; 30(4):423 - 423. DOI:10.1002/uog.4288 · 3.14 Impact Factor
  • Human Genetics 05/2007; 121(2):288. · 4.52 Impact Factor
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    ABSTRACT: Coffin-Lowry syndrome (CLS) is an X-linked mental retardation syndrome caused by defects in the RSK2 gene. We have identified a CLS family with four patients in two generations. The patients in this family, a mother and her three children (a male and two females), all have severe mental retardation with the typical CLS phenotype. In addition, brain MRI studies on the three siblings revealed abnormalities in deep subcortical white matter, thinning of the corpus callosum, hypoplastic cerebellar vermis, and asymmetry of the lateral ventricles. The degree of severity of the MRI findings correlated with the severity of mental retardation in the patients. Extensive mutation screening was performed on the entire RSK2 gene in this family. Twenty-two exons including the intron/exon junctions were amplified by PCR and subsequently sequenced on both strands. A novel mutation, a two-nucleotide insertion (298 ins TG), was identified. The insertion creates a stop codon at codon 100, resulting in a 99 amino acid truncated RSK2 protein. All patients tested have the same mutation, and no other mutation could be found in the RSK2 gene from the proband. The mutation was confirmed by PCR/RFLP. X-chromosome inactivation assay on the female patients revealed significant skewing toward inactivation of the normal RSK2 allele. Thus, this novel mutation is likely to be responsible for the unusual clinical presentation in this family, which includes full phenotypic expression in females and unique brain MRI abnormalities. The pathological function of the mutation and genotype/phenotype correlation between the mutation and this unusual clinical presentation await further clarification.
    American Journal of Medical Genetics Part A 06/2006; 140(12):1274-9. DOI:10.1002/ajmg.a.31266 · 2.05 Impact Factor
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    Wladimir Wertelecki
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    ABSTRACT: Birth defects (BD) surveillance using international standards was introduced in Ukraine by a network of five BD centers located in northwestern, central and southern regions. BD centers provide resources to access current and comprehensive information and to nurture partnerships with physicians, administrators, parental support groups, educators, and humanitarian assistance organizations. One outcome was the vigorous and popular website International BD Information Systems (IBIS). The network is now incorporated as OMNI-Net Ukraine. The program has documented high prevalence rates of neural tube defects (NTD); fetal alcohol effects (FAE); and idiopathic developmental retardation among orphans that prompted prevention and amelioration initiatives. Further program objectives include: universal folic acid flour fortification, as recommended by the Ukrainian Academy of Medicine; continued research on methods to reduce FAE in collaboration with partners from California; opening other early infant stimulation centers funded by local authorities, modeled on those in Rivne and Lutsk; and linking BD prevention with bioethical considerations, which is a topic of interest in Ukraine in part enhanced by the effects of Chornobyl.
    Journal of applied genetics 02/2006; 47(2):143-9. DOI:10.1007/BF03194614 · 1.90 Impact Factor
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    ABSTRACT: Oral consumption of synthetic folic acid can prevent neural tube defects (NTDs), which are some of the most severe congenital anomalies. The prevalence of NTDs in Ukraine and other countries of the former U.S.S.R. has not been well studied. We determined the prevalence of NTD-affected pregnancies in Northwestern Ukraine as background for policy decisions related to flour fortification in this country. The Ukrainian-American Birth Defects Program was established in 1999 and conducts population- based surveillance of birth defects in several oblasts (states) of Ukraine. We determined the prevalence of NTDs in the Volyn and Rivne oblasts of Northwestern Ukraine for three years, 2000-2002. There were 75,928 births in the two oblasts in 2000-2002. There were 159 cases of NTDs among live births, stillbirths, and induced abortions. The prevalence of NTDs in the two oblasts in Northwestern Ukraine is 2.1 per 1000 births. The prevalence of NTD-affected pregnancies we found in Northwestern Ukraine is almost four times what it should be. This prevalence suggests that population folate deficiency is widespread in Ukraine. Universal folic acid fortification of flour milled in Ukraine is urgently needed to end this epidemic of birth defects. Such fortification would be expected to prevent folate deficiency anemia, heart attacks, and strokes.
    Birth Defects Research Part A Clinical and Molecular Teratology 06/2004; 70(6):400-2. DOI:10.1002/bdra.20020 · 2.21 Impact Factor
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    ABSTRACT: A four-month-old white female, who was referred to us for genetic evaluation because of severe developmental delay, dysmorphic features, and bilateral cataracts, was found by routine cytogenetic analysis to have ring chromosome 16 in almost all cells analyzed. Ring chromosome 16 was confirmed and further delineated by fluorescence in situ hybridization (FISH). Breakpoints between loci D16S521 and KG8 on the short arm and D16S3121 and D16S303 on the long arm of chromosome 16 were determined by polymerase chain reaction (PCR) analysis. The deleted chromosome was of maternal origin. To our knowledge, this is the first case of ring chromosome 16 associated with bilateral cataracts. Comparison of previously reported cases with deletion of chromosome 16 and our case suggests the presence of cataract locus within 1 Mb of the terminus of 16q.
    American Journal of Medical Genetics 02/2002; 107(1):12-7. DOI:10.1002/ajmg.10091 · 3.23 Impact Factor
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    ABSTRACT: To illustrate the use of bacterial artificial chromosome (BAC) clone panels for molecular cytogenetic analysis of complex chromosome rearrangements (CCRs). High resolution cytogenetics followed by fluorescence in situ hybridization (FISH) analysis using chromosome band-specific BAC probes, in addition to commercially available probes. High resolution cytogenetics in conjunction with FISH using commercially available probes proved inadequate to resolve problems in characterizing a balanced CCR in the mother of a patient who had inherited an unbalanced form of the CCR. Accurate interpretation of the CCR and the unbalanced rearrangement in the patient as trisomy 7p12.2-->p21.3 was accomplished only through use of the BAC clone panel. Use of BAC clone panels can enhance the power of FISH analysis in defining chromosome rearrangements that cannot be resolved by high resolution chromosome analysis.
    Genetics in Medicine 01/2001; 3(2):126-31. · 6.44 Impact Factor
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    ABSTRACT: We report the case of a boy with achondroplasia and i(21q) Down syndrome. Besides craniofacial features typical in Down syndrome, the skeletal findings of achondroplasia dominate the clinical picture. The diagnosis of Down syndrome was based on clinical features and the cytogenetic finding of i(21q) trisomy 21. The diagnosis of achondroplasia was based on the presence of clinical and radiographic findings and confirmed by the presence of a common FGFR3 gene mutation (Gly380Arg) detected by restriction enzyme analysis and sequencing of the polymerase chain reaction products. This is the first report of achondroplasia associated with i(21q) Down syndrome.
    Southern Medical Journal 07/2000; 93(6):622-4. DOI:10.1097/00007611-200093060-00019 · 1.12 Impact Factor