"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.
[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 · 2.19 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To integrate knowledge on the embryologic and molecular basis of optic fissure closure with clinical observations in patients with uveal coloboma.
Closure of the optic fissure has been well characterized and many genetic alterations have been associated with coloboma; however, molecular mechanisms leading to coloboma remain largely unknown. In the past decade, we have gained better understanding of genes critical to eye development; however, mutations in these genes have been found in few individuals with coloboma. CHD7 mutations have been identified in patients with CHARGE syndrome (coloboma, heart defects, choanal atresia, retarded growth, genital anomalies, and ear anomalies or deafness). Animal models are bringing us closer to a molecular understanding of optic fissure closure.
Optic fissure closure requires precise orchestration in timing and apposition of two poles of the optic cup. The relative roles of genetics and environment on this process remain elusive. While most cases of coloboma are sporadic, autosomal dominant, autosomal recessive, and X-linked inheritance patterns have been described. Genetically, colobomata demonstrate pleiotropy, heterogeneity, variable expressivity, and reduced penetrance. Coloboma is a complex disorder with a variable prognosis and requires regular examination to optimize visual acuity and to monitor for potential complications.
Current Opinion in Ophthalmology 11/2006; 17(5):447-70. DOI:10.1097/01.icu.0000243020.82380.f6 · 2.64 Impact Factor
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