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本文报道了一个X连锁非综合征型语后聋的中国家系,该家系的致聋基因定位于X染色体一个遗传间距为5.41cM、物理距离为15.1Mb的区域,与已知的DFN2位点重叠。对此家系及以前报道的3个国内外DFN2家系进行PRPS1基因突变筛查,鉴定出PRPS1基因的4种不同错义突变。通过对酶分子结构的分析,及来自于患者的红细胞和成纤维细胞的体外酶活性测定,证实这些突变可导致磷酸核糖焦磷酸(PRPP)合成酶1活性下降。通过原位杂交,我们证实Prps1在小鼠的前庭和耳蜗毛细胞中皆有表达,并且在毛细胞中持续表达,出生后在螺旋神经节中仍有表达。PRPS1作为第二个X染色体上发现的非综合征型耳聋基因,是进行X连锁遗传性聋基因诊断很好的候选基因。
In this paper, we report a Chinese pedigree with deafness in X-linked non-syndromic type. The deafness gene of this family locates on the X chromosome with a genetic distance of 5.41cM and a physical distance of 15.1Mb, overlapping with the known DFN2 locus . To this family and previously reported three domestic and foreign DFN2 pedigree PRPS1 gene mutation screening identified four different PRPS1 gene missense mutations. Analysis of the molecular structure of the enzyme and the in vitro enzymatic activity of erythrocytes and fibroblasts from the patient confirmed that these mutations led to a decrease in the activity of phosphopentose pyrophosphate (PRPP) synthetase 1. By in situ hybridization, we confirmed that Prps1 is expressed both in the vestibular and cochlear hair cells of mice and persistently in hair cells, and is still expressed in the spiral ganglion after birth. PRPS1, a non-syndromic deafness gene found on the second X chromosome, is a good candidate for genetic diagnosis of X-linked hereditary deafness.