[Mitochondrial 12S rRNA A1555G mutation associated with nonsyndromic hearing loss in twenty-five Han Chinese pedigrees].
Mitochondrial 12S rRNA A1555AG mutation is one of the important causes of aminoglycoside-induced and nonsyndromic deafness. We report here the clinical, genetic and molecular characterization of 25 Chinese families carrying the A1555G mutation.Clinical and genetic characterizations of these Chinese families exhibited a wide range of penetrance, severity and age-at-onset of hearing impairment. The average penetrances of deafness were 28.1% and 21.5%, respectively, when aminoglycoside-induced hearing loss was included or excluded. Furthermore, the average age-of-onset for deafness without aminoglycoside exposure ranged from 1 and 15 years old. Their mitochondrial genomes exhibited distinct sets of polymorphisms including 16 novel variants, belonging to ten Eastern Asian haplogroups A, B, D, F, G, M, N and R, respectively. Strikingly, these Chinese families carrying mitochondrial haplogroup B exhibited higher penetrance and expressivity of hearing loss. In addition, 7 known secondary mutations and 21 variants resided at the highly conservative residues may enhance the penetrace of hearing loss in these Chinese families. Moreover, the absence of mutation in GJB2 gene suggested that GJB2 may not be a modifier for the phenotypic expression of the A1555G mutation in these Chinese families. These observations suggested that mitochondrial haplotypes and other modifiers may modulate the variable penetrance and expressivity of deafness among these Chinese families.
Department of Otolaryngology, Yuying Children's Hospital of Wenzhou Medical College, Wenzhou, China. gusdy13x@163.com
Guang-Hua
GH
Peng
Bin-Jiao
BJ
Zheng
Fang
F
Fang
Yue
Y
Wu
Ling-Zhi
LZ
Liang
Jing
J
Zheng
Ben-Yu
BY
Nan
Xiao
X
Yu
Xiao-Wen
XW
Tang
Yi
Y
Zhu
Jian-Xin
JX
Lu
Bo-Bei
BB
Chen
Min-Xin
MX
Guan
D000595:Amino Acid Sequence; D044466:Asian People / Q000208:ethnology / Q000235:genetics*; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D002681:China / Q000208:ethnology; D000072259:Connexin 26; D017630:Connexins; D004272:DNA, Mitochondrial / Q000737:chemistry / Q000235:genetics; D005260:Female; D034381:Hearing Loss / Q000208:ethnology / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D009690:Nucleic Acid Conformation; D010375:Pedigree; D012335:RNA, Ribosomal / Q000737:chemistry / Q000235:genetics*
D017630:Connexins; D004272:DNA, Mitochondrial; C000607042:GJB2 protein, human; D012335:RNA, Ribosomal; C075526:RNA, ribosomal, 12S; D000072259:Connexin 26