Bork J M, Peters L M, Riazuddin S, Bernstein S L, Ahmed Z M, Ness S L, Polomeno R, Ramesh A, Schloss M, Srisailpathy C R, Wayne S, Bellman S, Desmukh D, Ahmed Z, Khan S N, Kaloustian V M, Li X C, Lalwani A, Riazuddin S, Bitner-Glindzicz M, Nance W E, Liu X Z, Wistow G, Smith R J, Griffith A J, Wilcox E R, Friedman T B, Morell R J
Laboratory of Molecular Genetics, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Rockville, MD 20850, USA.
Am J Hum Genet. 2001 Jan;68(1):26-37. doi: 10.1086/316954. Epub 2000 Nov 21.
Genes causing nonsyndromic autosomal recessive deafness (DFNB12) and deafness associated with retinitis pigmentosa and vestibular dysfunction (USH1D) were previously mapped to overlapping regions of chromosome 10q21-q22. Seven highly consanguineous families segregating nonsyndromic autosomal recessive deafness were analyzed to refine the DFNB12 locus. In a single family, a critical region was defined between D10S1694 and D10S1737, approximately 0.55 cM apart. Eighteen candidate genes in the region were sequenced. Mutations in a novel cadherin-like gene, CDH23, were found both in families with DFNB12 and in families with USH1D. Six missense mutations were found in five families with DFNB12, and two nonsense and two frameshift mutations were found in four families with USH1D. A northern blot analysis of CDH23 showed a 9.5-kb transcript expressed primarily in the retina. CDH23 is also expressed in the cochlea, as is demonstrated by polymerase chain reaction amplification from cochlear cDNA.
导致非综合征性常染色体隐性耳聋（DFNB12）以及与色素性视网膜炎和前庭功能障碍相关的耳聋（USH1D）的基因，先前已被定位到10号染色体q21 - q22的重叠区域。对7个分离非综合征性常染色体隐性耳聋的高度近亲家庭进行了分析，以精确定位DFNB12基因座。在一个家族中，确定了一个关键区域位于D10S1694和D10S1737之间，相距约0.55厘摩。对该区域的18个候选基因进行了测序。在患有DFNB12的家庭和患有USH1D的家庭中均发现了一个新的钙黏蛋白样基因CDH23的突变。在5个患有DFNB12的家庭中发现了6个错义突变，在4个患有USH1D的家庭中发现了2个无义突变和2个移码突变。CDH23的Northern印迹分析显示有一个9.5kb的转录本，主要在视网膜中表达。聚合酶链反应从耳蜗cDNA扩增证明CDH23也在耳蜗中表达。
