中华医学遗传学杂志
中華醫學遺傳學雜誌
중화의학유전학잡지
CHINESE JOURNAL OF MEDICAL GENETICS
2012年
4期
382-387
,共6页
龚莎莎%陈波蓓%彭光华%郑静%张婷%郑斌娇%方芳%张初琴%吕建新%管敏鑫
龔莎莎%陳波蓓%彭光華%鄭靜%張婷%鄭斌嬌%方芳%張初琴%呂建新%管敏鑫
공사사%진파배%팽광화%정정%장정%정빈교%방방%장초금%려건신%관민흠
氨基糖甙类抗生素%非综合征型耳聋%线粒体DNA%突变%单倍型
氨基糖甙類抗生素%非綜閤徵型耳聾%線粒體DNA%突變%單倍型
안기당대류항생소%비종합정형이롱%선립체DNA%돌변%단배형
Aminoglycoside antibiotics%Nonsyndromic hearng loss%Mitochondrial DNA%Mutations%Haplotype
Objective To evaluate the effect of mitochondrial DNA(mtDNA) secondary mutations,haplotypes,GJB2 gene mutations on phenotype of 1494C > T mutation,and to study the molecular pathogenic mechanism of maternally transmitted aminoglycoside-induced and nonsyndromic hearing loss.Methods Two Chinese Han pedigrees of maternally transmitted aminoglycoside induced and nonsyndromic hearing loss were collected.The two probands and their family members underwent clinical,genetic and molecular evaluations including audiological examinations and mutational analysis of mitochondrial genome and GJB2 gene.Results Clinical evaluation revealed wide range of severity,age-at-onset and audiometric configuration of hearing impairment in matrilineal relatives in both families,for which the penetrance of hearing loss was respectively 42.9 % and 28.6% when aminoglycoside-induced deafness was included.When the effect of aminoglycosides was excluded,the penetrances of hearing loss were 14.3% and 14.3%.Sequence analysis of mitochondrial genomes identified a known 12S rRNA 1494C>T mutation,in addition with distinct sets of mtDNA polymorphisms belonging to Eastern Asian haplogroups C4a1a and B4b1c,respectively.Conclusion Mitochondrial 12S rRNA 1494C>T mutation probably underlie the deafness in both families.Lack of significant mutation in the GJB2 gene ruled out involvement of GJB2 in the phenotypic expression.However,aminoglycosides and other nuclear modifier genes may still modify the phenotype of the 1494C>T mutation in these families.The B4b1c is a newly identified haplogroup in aminoglycoside-induced and nonsyndromic hearing loss family carrying the 1494C>T mutation.The 1494C>T mutation seems to have occurred sporadically through evolution.