LINKAGE OF AUTOSOMAL-DOMINANT HEARING-LOSS TO THE SHORT ARM OF CHROMOSOME-1 IN 2 FAMILIES
LINKAGE OF AUTOSOMAL-DOMINANT HEARING-LOSS TO THE SHORT ARM OF CHROMOSOME-1 IN 2 FAMILIES
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DOI：
10.1056/nejm199408183310702
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发表时间：
1994-08-18
影响因子：
158.5
通讯作者：
WILLEMS, PJ
中科院分区：
文献类型：
--
作者：
COUCKE, P;VANCAMP, G;WILLEMS, PJ
背景。至少一半的早发性重度耳聋病例是由遗传因素引起的，但目前已发现的遗传缺陷却很少。对于最常见的遗传性耳聋来说尤其如此，这种耳聋是在没有任何相关综合征的情况下发生的。方法。我们研究了一个印度尼西亚大家庭，其中听力损失以常染色体显性遗传模式遗传。听力损失首先在青少年或二十几岁时影响高频，并在 10 年内变得严重。为了找到相关基因，我们使用分布在整个基因组上的微卫星标记进行了遗传连锁分析。然后，我们对具有相似遗传性听力损失模式的美国家庭和荷兰家庭进行了连锁分析。结果。在印度尼西亚大家族中，与耳聋相关的基因映射到染色体 Ip，多点杆得分超过 7。在美国家庭中，耳聋与染色体 1p 上的相同基因座相关，多点杆得分超过 5。然而，在荷兰家庭中，该基因座被排除。侧翼标记D1S255和D1S211在1p染色体上定义了一个6cM的区域，该区域可能包含与前两个家族中耳聋相关的基因。结论。在一些患有早发性常染色体显性听力损失的家族中，负责的基因位于染色体 1p 上。
Background. At least half of the cases of profound deafness of early onset are caused by genetic factors, but few of the genetic defects have been identified. This is particularly true of the most common hereditary forms of deafness, which occur in the absence of any associated syndrome.Methods. We studied a large Indonesian family in which hearing loss was inherited in an autosomal dominant pattern. The hearing loss first affects the high frequencies during the teens or 20s and becomes profound within 10 years. To locate the responsible gene, we performed genetic-linkage analysis, using microsatellite markers distributed over the entire genome. We then performed linkage analyses in an American family and a Dutch family with similar patterns of hereditary hearing loss.Results. In the extended Indonesian family, a gene linked to deafness mapped to chromosome Ip, with a multipoint rod score of more than 7. In the American family, deafness was linked to the same locus on chromosome 1p, with a multipoint rod score of more than 5. In the Dutch family, however, this locus was ruled out. The flanking markers D1S255 and D1S211 defined a region of 6 cM on chromosome 1p that is likely to contain the gene associated with deafness in the first two families.Conclusions. In some families with early-onset autosomal dominant hearing loss, the responsible gene is on chromosome 1p.