[Sequence analysis of the connexin 26 genes from a deafness family with A1555G mutation in Huaiyin].
OBJECTIVE
To ascertain whether connexin 26 (Cx26) gene was a nuclear modifier gene in an extensive family with matrilineal nonsyndromic deafness associated with A1555G mutation in Huaiyin, China.


METHODS
Following PCR-restriction fragment length polymorphism (PCR-RFLP) with ApaI restriction enzyme, Cx26 genes from 26 cases, with A1555G mitochondrial mutations in this family, and 62 controls (including 2 patrilineal relatives, 10 spouse controls and 50 unrelated controls), were sequenced.


RESULTS
Compared with the reference sequence of Cx26 gene, totally four kinds of nucleotide changes,79G -->A, 109G-->A, 341G-->A and 235delC, were detected in a heterozygous form. However, the former three were previously reported polymorphisms, and only the 235delC was a previously described recessive mutation associated with most autosomal nonsyndromic sensorineural hearing loss in Japan and China. Further study showed that the heterozygous 235delC mutation existed in both one individual with mild hearing loss and two individuals with normal hearing. Clinical characterization showed that 235delC mutation did not seem to modify the deafness phenotype due to the A1555G mutation. Moreover, this 235delC mutation was deduced to derive from a married-in control. Finally, there were no co-segregation between the phenotypes of hearing loss and the genotypes for Cx26 genes based on the four kinds of nucleotide changes.


CONCLUSIONS
The heterozygous 235delC mutation of the Cx26 gene may not modulate the severity of hearing loss associated with A1555G mutation and Cx26 gene is unlikely to be a modifier gene for hearing loss due to A1555G mitochondrial mutation in this Chinese family.
Zhang
Hai-Jun
HJ
Genetics Research Center, School of Medicine, Southeast University, Nanjing 210009, China.
Xu
Chun-Hong
CH
Zhang
Yi-Ju
YJ
Zhao
Su-Ying
SY
Geng
Xue-Xia
XX
Shan
Yun-Feng
YF
Fan
Gang
G
Xing
Guang-Qian
GQ
Shan
Xiang-Nian
XN
Bu
Xing-Kuan
XK
D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D002681:China / Q000453:epidemiology; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics*; D003638:Deafness / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D012150:Polymorphism, Restriction Fragment Length; D017421:Sequence Analysis; D055815:Young Adult
D017630:Connexins; C000607042:GJB2 protein, human; D000072259:Connexin 26