Mutations in the Cx26 (GJB2) gene have been shown to be responsible for a major part of autosomal recessive non-syndromic inherited prelingual deafness. We have sequenced the coding region of GJB2 gene from 169 Taiwanese patients with prelingual deafness and 100 unrelated normal individuals. In the deaf patients, three mutations were found: two novel mutations, 551G?A, and 299-300delAT, and one previously described mutation, 235delC. Four previously reported polymorphisms, 79G?A, 109G?A, 341A?G, and 608T?C, were also found in both deaf patients and normal individuals and one new possible polymorphism, 558G?A, which was only found in a patient. Interestingly, we did not find the 35delG allele, which is commonly found in the Caucasian population, either in the patients or in normal individuals we examined. Our data also showed 235delC to be the most common type of mutation found in Cx26 mutants (approximately 57%). Therefore, based on our findings, we have developed a simple molecular test for the 235delC mutation and it should be of considerable help to those families to understand the cause of their children having the prelingual deafness.

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The authors report a Taiwanese family with autosomal recessive hyperekplexia. Two novel mutations, W96C (from the paternal allele) and R344X (from the maternal allele), which are located in exon 4 and exon 7 of the GLRA1 gene, were identified in this family. A series of electrophysiologic investigations were conducted in one of the probands, and the results suggest that the "startle center" is located subcortically.

A cytogenetic study was made on 341 mentally retarded children in the Provincial Nantou Rehabilitation Center for the Mentally Retarded and the St. Raphael Opportunity Center in Tainan. Of the 89 mentally retarded children with chromosomal abnormalities, 63 had Down syndrome, 13 had the fragile X [fra(X)] syndrome, and the remaining had other aneuploid constitutions. Family studies were possible for 2 of the 13 fra(X) probands. The results of this study illustrate the contribution of chromosomal abnormalities to the pathogenesis of mental retardation in children.

The fibrillin-1 gene (FBN1) mutations are associated with a broad spectrum of disorders including Marfan syndrome (MFS) and show great clinical heterogeneity. An underrepresentation for mutations leading to premature termination codon (PTC) in FBN1 exons 24-32 was found in neonatal or severe MFS but the underlying cause was unclear. This study thoroughly examined two FBN1 mutations on exons 24-32 region to illustrate the molecular mechanisms underlying these FBN1 mutations on MFS etiology. Two nucleotide substitutions, c.3208G> C, the last nucleotide of exon 26, and c.3209A>G, the first nucleotide of exon 27, affecting the same amino acid, p.D1070H and p.D1070G, respectively, gave very different phenotypes. We demonstrate that c.3208G>C generates two alternatively spliced transcripts, while c.3209A>G does not affect the splicing. We further demonstrate that the aberrantly spliced transcripts do not go through nonsense-mediated decay, but rather produce unstable, premature protein peptides that are degraded by endoplasmic reticulum associated degradation. The molecular mechanism outlined here defines a model for the pathogenesis of PTC-containing mutation within the exons 24-32 of FBN1 in MFS. Furthermore, our data suggest that PTC mutation within this region may lead to early lethality in neonatal MFS.