Van Camp Guy, Coucke Paul J, Akita Jiro, Fransen Erik, Abe Satoko, De Leenheer Els M R, Huygen Patrick L M, Cremers Cor W R J, Usami Shin-Ichi
Department of Medical Genetics, University of Antwerp-UIA, Antwerp, Belgium.
Hum Mutat. 2002 Jul;20(1):15-9. doi: 10.1002/humu.10096.
Several different mutations in the KCNQ4 K+ channel gene are responsible for autosomal dominant nonsyndromic hearing impairment (DFNA2). Here we describe two additional families originating from Europe and Japan with a KCNQ4 missense mutation (W276S) that was previously found in one European family. We compared the disease-associated haplotype of the three W276S-bearing families using closely linked microsatellite markers and intragenic single nucleotide polymorphisms. Differences between the haplotypes were found, excluding a single founder mutation for the families. Therefore, the W276S mutation has occurred three times independently, and most likely represents a hot spot for mutation in the KCNQ4 gene.
KCNQ4钾离子通道基因中的几种不同突变是常染色体显性非综合征性听力障碍（DFNA2）的病因。在此，我们描述了另外两个分别来自欧洲和日本的家族，它们携带一种先前在一个欧洲家族中发现的KCNQ4错义突变（W276S）。我们使用紧密连锁的微卫星标记和基因内单核苷酸多态性，比较了这三个携带W276S突变家族的疾病相关单倍型。发现这些单倍型之间存在差异，排除了这些家族存在单一始祖突变的可能性。因此，W276S突变已独立发生了三次，很可能代表了KCNQ4基因中的一个突变热点。
