Coucke P, Van Camp G, Djoyodiharjo B, Smith S D, Frants R R, Padberg G W, Darby J K, Huizing E H, Cremers C W, Kimberling W J
Department of Medical Genetics, University of Antwerp, Belgium.
N Engl J Med. 1994 Aug 18;331(7):425-31. doi: 10.1056/NEJM199408183310702.
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.
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.
In the extended Indonesian family, a gene linked to deafness mapped to chromosome 1p, with a multipoint lod score of more than 7. In the American family, deafness was linked to the same locus on chromosome 1p, with a multipoint lod 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.
In some families with early-onset autosomal dominant hearing loss, the responsible gene is on chromosome 1p.
至少一半的早发性重度耳聋病例是由遗传因素引起的，但已确定的遗传缺陷却很少。对于最常见的遗传性耳聋形式而言尤其如此，这些耳聋在没有任何相关综合征的情况下发生。
我们研究了一个大型印度尼西亚家庭，其中听力损失以常染色体显性模式遗传。听力损失在十几岁或二十多岁时首先影响高频，并在10年内发展为重度耳聋。为了定位致病基因，我们使用分布在整个基因组中的微卫星标记进行了基因连锁分析。然后我们在美国和荷兰的两个具有相似遗传性听力损失模式的家庭中进行了连锁分析。
在这个印度尼西亚大家庭中，一个与耳聋相关的基因定位于1号染色体短臂，多点连锁分析计分超过7。在美国的家庭中，耳聋与1号染色体短臂上的相同位点相关，多点连锁分析计分超过5。然而，在荷兰家庭中，这个位点被排除。侧翼标记D1S255和D1S211在1号染色体短臂上确定了一个6厘摩的区域，在前两个家庭中这个区域可能包含与耳聋相关的基因。
在一些早发性常染色体显性听力损失的家庭中，致病基因位于1号染色体短臂上。
