A new locus (DFNA47) for autosomal dominant non-syndromic inherited hearing loss maps to 9p21-22 in a large Italian family
A new locus (DFNA47) for autosomal dominant non-syndromic inherited hearing loss maps to 9p21-22 in a large Italian family
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DOI：
10.1038/sj.ejhg.5200929
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发表时间：
2003-02-01
影响因子：
5.2
通讯作者：
Gasparini, P
中科院分区：
文献类型：
--
作者：
D'Adamo, P;Donaudy, F;Gasparini, P
听力损失是人类最常见的感觉障碍，遗传因素是主要原因。大约15-20%的遗传病例表现出常染色体显性遗传模式。迄今为止，已定位了41个常染色体显性基因座，鉴定了17个基因。在这里，我们报告了一个新的常染色体显性遗传非综合征性听力损失，DFNA 47，染色体9 p21 -22在一个大型的多代意大利家庭进行性听力障碍基因座的映射。大多数受影响的人在十几岁后注意到听力障碍，随后逐渐发展为中度至重度损失。无明显前庭功能障碍及其他相关异常。经过全基因组搜索后，标记D9 S157（theta=0）获得的最大lod评分为3.14。对其他标记物的研究使我们能够以3.58（来自D9 S285的θ =0处）和3.67（来自D9 S162的θ =0处）的阳性lod得分确认该区域。突变体定义了侧翼为标记D9 S268和D9 S942的约9 cM的区域。多点连锁分析显示Lod得分为4.26。很少有已知的基因映射到该区域，那些可能与听力功能相关的基因正在筛选致病突变。
Hearing loss is the most common sensory disorder in humans, and genetic factors are a major cause. Approximately 15-20% of genetic cases exhibit an autosomal dominant pattern of transmission. So far, 41 autosomal dominant loci have been mapped and 17 genes have been identified. Here we report the mapping of a novel locus for autosomal dominant non-syndromic hearing loss, DFNA47, to chromosome 9p21-22 in a large multigenerational Italian family with progressive hearing impairment. Most affected individuals noticed hearing impairment after their teens with subsequent gradual progression to a moderate-severe loss. There were no obvious vestibular dysfunction and other associated abnormalities. A maximum lod score of 3.14 was obtained with marker D9S157 (at theta=0) after a genome wide search. The study of additional markers allowed us to confirm this region with positive lod scores of 3.58 (at theta=0 from D9S285) and of 3.67 (at theta=0 from D9S162). Recombinants define a region of approximately 9 cM flanked by markers D9S268 and D9S942. Multipoint linkage analysis showed a Lod score of 4.26. Few known genes map to the region, and those possibly related by function to hearing are being screened for disease-causing mutations.