Publications (110) View all
-
Article: Reproductive patterns among mothers of males diagnosed with Duchenne or Becker muscular dystrophy.
[show abstract] [hide abstract]
ABSTRACT: Diagnosis of a child with Duchenne or Becker muscular dystrophy (DBMD) may impact future maternal reproductive choice; however, little is known about the reproductive patterns of mothers with a male child diagnosed with DBMD. Using population-based surveillance data collected by the muscular dystrophy surveillance, tracking, and research network, the proportion of mothers who conceived and delivered a live birth following the diagnosis of DBMD in an affected male child and factors associated with such reproductive choice were identified. To accomplish this, maternal demographic data were linked to birth certificate data to construct the reproductive history for 239 mothers. Univariable and bivariable analyses were conducted to determine the proportion of mothers delivering a live birth and associated factors. By the time of the current study, 96 (40.2%) of the 239 mothers had at least one live birth following delivery of their oldest affected male child; 53 (22.2%) of these mothers had a live birth before and 43 (18.0%) had a live birth after DBMD diagnosis of a male child. Mothers with a live birth after diagnosis were significantly younger at diagnosis of the oldest affected male child (26.2 ± 4.2 years vs. 31.5 ± 5.5 years), and were less likely to be white non-Hispanic compared to those with no live birth after diagnosis. These results suggest that about one in five mothers deliver a live birth subsequent to DBMD diagnosis in a male child. Maternal age and race/ethnicity were associated with this reproductive choice. © 2012 Wiley Periodicals, Inc.American Journal of Medical Genetics Part A 12/2012; · 2.39 Impact Factor -
Article: A genome-wide association study identifies susceptibility loci for nonsyndromic sagittal craniosynostosis near BMP2 and within BBS9.
[show abstract] [hide abstract]
ABSTRACT: Sagittal craniosynostosis is the most common form of craniosynostosis, affecting approximately one in 5,000 newborns. We conducted, to our knowledge, the first genome-wide association study for nonsyndromic sagittal craniosynostosis (sNSC) using 130 non-Hispanic case-parent trios of European ancestry (NHW). We found robust associations in a 120-kb region downstream of BMP2 flanked by rs1884302 (P = 1.13 × 10(-14), odds ratio (OR) = 4.58) and rs6140226 (P = 3.40 × 10(-11), OR = 0.24) and within a 167-kb region of BBS9 between rs10262453 (P = 1.61 × 10(-10), OR = 0.19) and rs17724206 (P = 1.50 × 10(-8), OR = 0.22). We replicated the associations to both loci (rs1884302, P = 4.39 × 10(-31) and rs10262453, P = 3.50 × 10(-14)) in an independent NHW population of 172 unrelated probands with sNSC and 548 controls. Both BMP2 and BBS9 are genes with roles in skeletal development that warrant functional studies to further understand the etiology of sNSC.Nature Genetics 11/2012; · 35.53 Impact Factor -
Article: A genome-wide association study identifies susceptibility loci for nonsyndromic sagittal craniosynostosis near BMP2 and within BBS9
[show abstract] [hide abstract]
ABSTRACT: Sagittal craniosynostosis is the most common form of craniosynostosis, affecting approximately one in 5,000 newborns. We conducted, to our knowledge, the first genome-wide association study for nonsyndromic sagittal craniosynostosis (sNSC) using 30 non-Hispanic case-parent trios of European ancestry (NHW). We found robust associations in a 20-kb region downstream of BMP2 flanked by rs884302 (P = .3 × 0 −4 , odds ratio (OR) = 4.58) and rs640226 (P = 3.40 × 0 − , OR = 0.24) and within a 67-kb region of BBS9 between rs0262453 (P = .6 × 0 −0 , OR = 0.9) and rs7724206 (P = .50 × 0 −8 , OR = 0.22). We replicated the associations to both loci (rs884302, P = 4.39 × 0 −3 and rs0262453, P = 3.50 × 0 −4) in an independent NHW population of 72 unrelated probands with sNSC and 548 controls. Both BMP2 and BBS9 are genes with roles in skeletal development that warrant functional studies to further understand the etiology of sNSC. Skull development is a complex process that involves ongoing inter action between the bones of the skull and cranial soft tissues. The cranial vault is comprised of intramembranous bones joined by sutures of dense fibrous tissue that accommodate the growing brain. Bone is added at these sutures during growth, and the skull eventu ally ossifies completely. Craniosynostosis, the premature closure of one or more of the cranial vault sutures, is a common congenital anomaly. Approximately 80% of craniosynostosis occurs as an iso lated anomaly, called nonsyndromic craniosynostosis (NSC), with out major associated malformations 1 . Rare mutations in the FGFR2, TWIST1, FREM1, LRIT3, EFNA4 and RUNX2 duplications have been reported in a minor fraction of individuals with NSC 2–9 . The remain der (~20%) of craniosynostosis cases are syndromic, occurring with one or more additional major malformations caused by singlegene mutations in one of at least eight genes (FGFR1, FGFR2, FGFR3, TWIST1, EFNB1, POR, MSX2 and RAB23), involving primarily the coronal sutures 10–12 . The most common type of NSC is sNSC, which accounts for 40–58% of all cases 13,14 . The etiology of sNSC is not well understood; however, the published literature suggests that it is a multifactorial condition in which both genetic and environmental factors have a role, as indicated by a higher rate of concordance in monozygotic as compared to dizygotic twins (30% compared to 0%, respectively) 15 , A genomewide association study identifies susceptibility loci for nonsyndromic sagittal craniosynostosis near BMP2 and within BBS9Nature Genetics 11/2012; · 35.53 Impact Factor -
Article: Maternal Occupational Exposure to Polycyclic Aromatic Hydrocarbons and Risk of Oral Cleft-Affected Pregnancies.
[show abstract] [hide abstract]
ABSTRACT: Objective : To evaluate whether there is an association between maternal occupational exposure to polycyclic aromatic hydrocarbons and oral clefts in offspring. This is the first human study of polycyclic aromatic hydrocarbons and clefts of which the authors are aware. Design : Case-control study. Setting, Participants : Data for 1997 to 2002 from the National Birth Defects Prevention Study, a large population-based case-control study in the United States, were analyzed. Maternal telephone interviews yielded information on jobs held in the month before through 3 months after conception. Two industrial hygienists independently assessed occupational exposure to polycyclic aromatic hydrocarbons; all jobs rated as exposed or with rating difficulty were reviewed with a third industrial hygienist to reach consensus on all exposure parameters. Logistic regression estimated crude and adjusted odds ratios with 95% confidence intervals for cleft lip with or without cleft palate and cleft palate alone. Results : There were 2989 controls (3.5% exposed), 805 cases of cleft lip with or without cleft palate (5.8% exposed), and 439 cases of cleft palate alone (4.6% exposed). The odds of maternal occupational exposure to polycyclic aromatic hydrocarbons (any versus none) during pregnancy was increased for cleft lip with or without cleft palate cases as compared with controls (odds ratio, 1.69; 95% confidence interval, 1.18 to 2.40); the odds ratio was 1.47 (95% confidence interval 1.02 to 2.12) when adjusted for maternal education. There was a statistically significant adjusted exposure-response relationship for cleft lip with or without cleft palate (P(trend) = .02). Odd ratios for cleft palate alone were not statistically significant. Conclusions : Maternal occupational exposure to polycyclic aromatic hydrocarbons was associated with increased risk of cleft lip with or without cleft palate in offspring.The Cleft Palate-Craniofacial Journal 11/2012; · 0.82 Impact Factor -
Article: Hirschsprung's disease and variants in genes that regulate enteric neural crest cell proliferation, migration and differentiation.
[show abstract] [hide abstract]
ABSTRACT: Hirschsprung's disease (HSCR) results from failed colonization of the embryonic gut by enteric neural crest cells (ENCCs); colonization requires RET proto-oncogene (RET) signaling. We sequenced RET to identify coding and splice-site variants in a population-based case group and we tested for associations between HSCR and common variants in RET and candidate genes (ASCL1, homeobox B5 (HOXB5), L1 cell adhesion molecule (L1CAM), paired-like homeobox 2b (PHOX2B), PROK1 and PROKR1) chosen because they are involved in ENCC proliferation, migration and differentiation in animal models. We conducted a nested case-control study of 304 HSCR cases and 1215 controls. Among 38 (12.5%) cases with 34 RET coding and splice-site variants, 18 variants were previously unreported. We confirmed associations with common variants in HOXB5 and PHOX2B but the associations with variants in ASCL1, L1CAM and PROK1 were not significant after multiple comparisons adjustment. RET variants were strongly associated with HSCR (P-values between 10(-3) and 10(-31)) but this differed by race/ethnicity: associations were absent in African-Americans. Our population-based study not only identified novel RET variants in HSCR cases, it showed that common RET variants may not contribute to HSCR in all race/ethnic groups. The findings for HOXB5 and PHOX2B provide supportive evidence that genes regulating ENCC proliferation, migration and differentiation could be risk factors for HSCR.Journal of Human Genetics 05/2012; 57(8):485-93. · 2.57 Impact Factor
