[Mutation analysis of GJB2, GJB3 and GJB6 gene in deaf population from special educational school of Chifeng city].
OBJECTIVE
To investigate the genetic causes of nonsyndromic 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.


METHODS
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 bi allele mutation and probands who were diagnosed as enlarged vestibular aqueduct by temporal CT), GJB3 gene mutation was analyzed by direct sequencing for its exon.


RESULTS
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 pathogenetic 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 pathogenetic mutation of GJB3 gene. one of whom also carried GJB2 235delC heterozygous mutation. One subjects in the control group carried pathogenetic mutation of GJB3 gene. Three types of novel variants of GJB3 gene were found.


CONCLUSIONS
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.
Yuan
Yongyi
Y
Department of Otolaryngology-Head and Neck Surgery, Otorhinolaryngology Institute, Genetic Testing Center for Deafness, PLA General Hospital, Beijing, 100853, China.
Huang
Deliang
D
Dai
Pu
P
Zhu
Xiuhui
X
Yu
Fei
F
Zhang
Xin
X
Liu
Lixian
L
Han
Dongyi
D
D000293:Adolescent; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D002681:China; D000072259:Connexin 26; D000075302:Connexin 30; D017630:Connexins / Q000235:genetics*; D004252:DNA Mutational Analysis; D004519:Education, Special; D005260:Female; D005820:Genetic Testing; D005838:Genotype; D034381:Hearing Loss / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D008297:Male; D009154:Mutation; D011110:Polymorphism, Genetic; D013334:Students; D055815:Young Adult
D000075302:Connexin 30; D017630:Connexins; C000607042:GJB2 protein, human; C491020:GJB6 protein, human; D000072259:Connexin 26; C068044:GJB3 protein, human