Dominant modifier DFNM1 suppresses recessive deafness DFNB26
Dominant modifier DFNM1 suppresses recessive deafness DFNB26
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DOI：
10.1038/82558
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发表时间：
2000-12-01
期刊：
影响因子：
30.8
通讯作者：
Wilcox, ER
中科院分区：
文献类型：
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作者：
Riazuddin, S;Castelein, CM;Wilcox, ER
超过50%的严重儿童耳聋是由基因决定的，其中约70%没有其他异常，因此被称为非综合征性（1,2）。到目前为止，已经绘制了30个非综合征性隐性耳聋基因座，并在DFNB1、DFNB2、DFNB3、DFNB4、DFNB9和DFNB21 6个基因座上发现了缺陷基因，分别编码connexin-26（文献3）、myosin VIIA（文献4）、myosin XV（文献5）、pendrin(6)、otoferlin(7)和α -tectorin(8)。在这里，我们将一个新的隐性非综合征性耳聋位点DFNB26定位到一个近亲巴基斯坦家庭的染色体4q31的1.5 cm间隔上。在theta =0时，仅计算该家族中8个受影响个体时，D4S1610的杆值最高为8.10。有七个未受影响的家庭成员也是dfnb26连锁单倍型的纯合子，因此是非渗透的。一个显性修饰语，DFNM1。D1S2815在theta =0时的杆值为4.31，在染色体1q24上的5.6 cm区域定位。
More than 50% of severe childhood deafness is genetically determined, approximately 70% of which occurs without other abnormalities and is thus termed nonsyndromic(1,2). So far, 30 nonsyndromic recessive deafness loci have been mapped and the defective genes at 6 loci, DFNB1, DFNB2, DFNB3, DFNB4, DFNB9 and DFNB21, have been identified, encoding connexin-26 (ref. 3), myosin VIIA (ref. 4), myosin XV (ref. 5), pendrin(6) otoferlin(7) and alpha -tectorin(8), respectively. Here we map a new recessive nonsyndromic deafness locus, DFNB26, to a 1.5-cM interval of chromosome 4q31 in a consanguineous Pakistani family. A maximum rod score of 8.10 at theta =0 was obtained with D4S1610 when only the 8 affected individuals in this family were included in the calculation. There are seven unaffected family members who are also homozygous for the DFNB26-linked haplotype and thus are non-penetrant. A dominant modifier, DFNM1. that suppresses deafness in the 7 nonpenetrant individuals was mapped to a 5.6-cM region on chromosome 1q24 with a rod score of 4.31 at theta =0 for D1S2815.