Department of Otolaryngology-Head and Neck Surgery, Otorhinolaryngology Institute, Genetic Testing Center for Deafness, PLA General Hospital, Beijing, 100853, China.
OBJECTIVE: To investigate the genetic causes of nonsymdromic deaf patients in special educational school of Chifeng city. Inner Mongolia by genetic screening testing method. This study focused on analyzing mutations of coding sequence of GJB2, GJB3 and GJB6 gene. METHOD: DNA were extracted out from peripheral blood of 134 nonsyndromic deaf probands of Chifeng special educational school and 100 normal hearing controls in northern China. First, GJB2 gene mutation was analyzed by direct sequencing for its only exon in the open reading frame. Individuals found with heterozygous GJB2 mutation were given further testing for GJB6 del(GJB6-D13S1830) and direct sequencing for its exon. In 91 probands with unknown genetic cause (excluding probands who carried mtDNA A1555G mutation and GJB2 gene biallele mutation and probands who were diagnosed as enlarged vestibular aqueduct by temporal CT), GJB3 gene mutation was analyzed by direct sequencing for its exon. RESULT: The sequencing results revealed that forty-one cases carried GJB2 mutation. of which twenty-two were homozygous or compound heterozygous and nineteen were heterozygous. Further testing for GJB6 del(GJB6-D13S1830) and analysis of its coding sequence in GJB2 heterozygous cases showed no positive result. Four subjects in control group carried pathogentic mutation of GJB2 gene. Six types of novel variants of GJB2 gene were detected. Of the 91 deaf probands with unknown etiology. two probands were found carrying heterozygous pathogentic mutation of GJB3 gene. one of whom also carried GJB2 235delC heterozygous mutation. One subjects in the control group carried pathogentic mutation of GJB3 gene. Three types of novel variants of GJB3 gene were found. CONCLUSION: By screening GJB2.GJB3 and GJB6 gene, we found 32.1% probands carrying GJB2, GJB3, and GJB6 mutations and we are able to determine genetic cause related to these three genes from one family for 16.42 percent of nonsyndromic deaf probands in special educational school of Chifeng city. The discovery of novel variants of GJB2 and GJB3 gene makes the mutational and polymorphic spectrum more plentiful in Chinese population.