Gap junctions, which mediate rapid intercellular communication, consist of connexins, small transmembrane proteins that belong to a large family of proteins found throughout the species. Mutations in the GJB2 gene, encoding Connexin 26, can cause nonsyndromic autosomal recessive or dominant hearing loss with or without skin manifestations. A 3-yr-old Korean female and her mother presented to our clinic with diffuse hyperkeratosis of the palms and soles (May 3, 2007). Skin biopsies from the soles of both patients demonstrated histopathological evidence of palmoplantar keratoderma. The patient and a number of her maternal family members also had congenital hearing loss. The combination of congenital hearing loss and palmoplantar keratoderma, inherited as an autosomal dominant trait, led us to test for a mutation in the GJB2 gene in both patients. The results showed the R75W mutation of the GJB2 gene in both. In conclusion, the simultaneous occurrence of a GJB2 mutation in a mother and daughter suggests that R75W mutation cause autosomal dominant hearing loss presenting with palmoplantar keratoderma. To the best of our knowledge, this is the first report of a GJB2 mutation associated with syndromic autosomal dominant hearing loss and palmoplantar keratoderma in a Korean family.
Adult ; Alleles ; Amino Acid Substitution ; Child, Preschool ; Connexins/*genetics ; DNA Mutational Analysis ; Deafness/complications/*genetics ; Female ; Humans ; Keratoderma, Palmoplantar/complications/*genetics/pathology ; *Mutation ; Pedigree ; Skin/pathology

OBJECTIVETo determine the carrier rate for common mutations causing deafness among pregnant women in order to prevent births of deaf children.

METHODSFor 893 pregnant women, 2 mL peripheral venous blood was taken and DNA was extracted. A deafness DNA microarray screening was applied to such samples, and DNA sequencing was applied to husbands of women with positive screening results.

RESULTSA total of 40 carriers were detected, with the overall mutation rate being 4.48%. Among such carriers, GJB2 235delC was the most common heterozygous mutation (18 cases) and the mutation rate was 2.02%. GJB2 299A-T heterozygous mutation was detected in 7 cases with a mutation rate of 0.78%. IVS7-2A to G heterozygous mutation was detected in 9 cases with a mutation rate of 1.02%. There were 2 cases carrying GJB3 heterozygous mutation and 2 cases of mitochondrial 12S rRNA heterozygous mutation, with a mutation rate of 0.22%. IVS7-2A>G with GJB3 538C>T double heterozygous mutation was detected in 1 case, and IVS7-2A>G with GJB2 299A-T double heterozygous mutation was detected in another case, with the mutation rate of each being 0.11%. DNA sequencing has failed to find presence of mutations in the same gene in the husbands. The results of neonatal hearing follow-up were all normal.

CONCLUSIONApplications of the deaf genes screening in pregnant women may play prove to be valuable for the early detection for neonatal deafness.

Adult ; Connexin 26 ; Connexins ; genetics ; Deafness ; diagnosis ; embryology ; genetics ; prevention & control ; Female ; Genetic Testing ; Humans ; Mutation ; Pregnancy ; Pregnancy Complications ; diagnosis ; genetics ; Prenatal Diagnosis ; RNA, Ribosomal ; genetics ; Young Adult

OBJECTIVETo investigate the clinical characteristics and the prevalence of mitochondrial gene A3243G mutation in diabetic pedigrees.

METHODSNineteen suspected mitochondrial DNA diabetic family members from three families were recruited. The gene fragment was amplified by PCR, and mutation was detected by direct sequencing.

RESULTSIn three pedigrees, the three probands and their mothers were found carrying the most common nt3243A>G mutation. Most of diabetic patients in these families were deaf and diabetes was developed at early age, characterized by impaired beta cell function and low body mass index (BMI).

CONCLUSIONThe mitochondrial gene A3243G mutation may cause diabetes mellitus and deaf.

Adolescent ; Adult ; Aged ; Base Sequence ; DNA Mutational Analysis ; DNA, Mitochondrial ; genetics ; Deafness ; complications ; genetics ; Diabetes Complications ; genetics ; Diabetes Mellitus ; genetics ; Female ; Humans ; Male ; Middle Aged ; Mutation ; Pedigree ; RNA, Transfer, Leu ; genetics