"So, the natural question to ask would be whether methimazole may be associated with another very specific feature of CHARGE syndrome, coloboma of the eyes. Indeed, the author recently evaluated a newborn female who had been prenatally exposed to methimazole (Aramaki et al. 2005). The patient exhibited multiple anomalies, including vitelline duct anomalies and nipple hypoplasia. "
[Show abstract][Hide abstract] ABSTRACT: In this review, our work on CHARGE syndrome will be used to exemplify the role of rare cases in birth defects research. The analysis of 29 cases with mutations of CHD7, the causative gene for CHARGE syndrome, clarified the relative importance of the cardinal features, including facial nerve palsy and facial asymmetry. Concurrently, in situ hybridization using chick embryos studies were performed to delineate the expression pattern of Chd7. The Chd7-positive regions in the chick embryos and the anatomical defects commonly seen in patients with CHARGE syndrome were well correlated: expression in the optic placode corresponded with defects such as coloboma, neural tube with mental retardation, and otic placode with ear abnormalities. The correlation between expression in the branchial arches and nasal placode with the clinical symptoms of CHARGE syndrome, however, became apparent when we encountered two unique CHARGE syndrome patients: one with a DiGeorge syndrome phenotype and the other with a Kallman syndrome phenotype. A unifying hypothesis that could explain both the DiGeorge syndrome phenotype and the Kallman syndrome phenotype in patients with CHARGE syndrome may be that the mutation in CHD7 is likely to exert its effect in the common branch of the two pathways of neural crest cells. As exemplified in CHARGE syndrome research, rare cases play a critical role in deciphering the mechanisms of human development. Close collaboration among animal researchers, epidemiologists and clinicians hopefully will enhance and maximize the scientific value of rare cases.
"Methimazole (MMI) or its pre-drug Carbimazole (CMZ) are common antithyroid drugs; however, they have been related to the occurrence of congenital defects such as aplasia cutis congenita  , choanal atresia           , esophageal atresia    , facial features [2–5,7,10–13,16], athelia or hypotelia   , cardiovascular defects [6,7,14–16], mental retardation       and iridic and retinal coloboma  . A 'MMI embryopathy' has been suggested in all these reports. "
[Show abstract][Hide abstract] ABSTRACT: Thyrotoxicosis affects 0.2% of pregnant women and antithyroid drugs are the treatment of choice during pregnancy. Several case reports have suggested a relationship between the prenatal use of methimazole (MMI) and choanal atresia in the offspring. However, two epidemiological studies did not find an increased teratogenic risk for MMI. This multicenter case-control study compared the frequency of maternal hyperthyroidism treated with MMI during pregnancy, in children with choanal atresia (cases) and a control group randomly selected (three matched controls according to maternal age for each case). Mothers of cases (N = 61) and controls (N = 183) were interviewed for socio-demographic questions, obstetrical and genetic history, and exposure during pregnancy to different agents; specifically detailed information regarding hyperthyroidism and MMI intake was obtained. Prenatal exposure to maternal hyperthyroidism treated with MMI was identified in 10/61 cases (16.4%) compared to 2/183 (1.1%) in the control group (OR = 17.75; CI95% = 3.49-121.40). Cases and controls did not differ in their parental degree of education, paternal occupation, twinning, maternal parity, and other exposures during pregnancy. Facial features in exposed cases showed some similarities. Our data suggest that prenatal exposure to maternal hyperthyroidism treated with MMI is associated with choanal atresia. In addition, based on our cases and a critical literature review, we propose that the mother's disease might be the causal factor and not the MMI treatment.
American Journal of Medical Genetics Part A 10/2008; 146A(18):2390-5. DOI:10.1002/ajmg.a.32497 · 2.16 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We developed several approaches to direct determination of the 15N CSA from relaxation measurements in uniformly 15N-labeled proteins in solution. These methods are based on multiple-field measurements and could be extended to other nuclei in proteins and other molecules. Combined with the isotropic chemical shift measurements, this provides an experimental approach to full characterization of chemical shift tensors in proteins in their native milieu, which is likely to provide valuable information on the nature of chemical shifts and their relation to protein structure. Knowledge of 15N CSA is essential for an accurate characterization of protein dynamics from relaxation measurements.
Methods in Enzymology 02/2001; 339:109-26. DOI:10.1016/S0076-6879(01)39312-6 · 2.09 Impact Factor
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