Recurrent and Private MYO15A Mutations Are Associated with Deafness in the Turkish Population
Recurrent and Private MYO15A Mutations Are Associated with Deafness in the Turkish Population
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DOI：
10.1089/gtmb.2010.0039
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发表时间：
2010-08-01
影响因子：
1.4
通讯作者：
Tekin, Mustafa
中科院分区：
文献类型：
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作者：
Cengiz, F. Basak;Duman, Duygu;Tekin, Mustafa
在不同人群中与听力损失相关的MYO 15 A突变的身份和频率在很大程度上仍然未知。我们筛选MYO 15 A基因突变在104个无关的多重和血缘的土耳其家庭与常染色体隐性遗传非综合征感音神经性耳聋，使用同源性定位。对定位于DFNB 3基因座的10个家族中的MYO 15 A进行筛查，发现了5个以前未报告的突变：p.Y289X（1个家族）、p.V1400M（1个家族）、p.S1481P（1个家族）、p.R1937TfsX10（3个家族）和p.S3335AfsX121（2个家族）。复发性突变与保守的单倍型相关，表明存在创始人效应。在所有纯合子突变受试者中均观察到重度至极重度感音神经性听力损失，但一个家族的两名成员除外，他们在N-末端延伸结构域中的p.Y289X突变为纯合子，并具有相当大的残余听力。我们估计土耳其常染色体隐性遗传非综合征性耳聋患者纯合子MYO 15 A突变的患病率为0.062（95%置信区间为0.020-0.105）。
The identities and frequencies of MYO15A mutations associated with hearing loss in different populations remained largely unknown. We screened the MYO15A gene for mutations in 104 unrelated multiplex and consanguineous Turkish families with autosomal recessive nonsyndromic sensorineural hearing loss using autozygosity mapping. The screening of MYO15A in 10 families mapped to the DFNB3 locus revealed five previously unreported mutations: p.Y289X (1 family), p.V1400M (1 family), p.S1481P (1 family), p.R1937TfsX10 (3 families), and p.S3335AfsX121 (2 families). Recurrent mutations were associated with conserved haplotypes suggesting the presence of founder effects. Severe to profound sensorineural hearing loss was observed in all subjects with homozygous mutations except for two members of a family who were homozygous for the p.Y289X mutation in the N-terminal extension domain and had considerable residual hearing. We estimate the prevalence of homozygous MYO15A mutations in autosomal recessive nonsyndromic deafness in Turkey as 0.062 (95% confidence interval is 0.020-0.105).