Masmoudi Saber, Tlili Abdelaziz, Majava Marja, Ghorbel Abdel Monem, Chardenoux Sébastien, Lemainque Arnaud, Zina Zeineb Ben, Moala Jihene, Männikkö Minna, Weil Dominique, Lathrop Mark, Ala-Kokko Leena, Drira Mohamed, Petit Christine, Ayadi Hammadi
Laboratoire de Génétique Moléculaire Humaine, Faculté de Médecine Sfax, Tunisie.
Eur J Hum Genet. 2003 Feb;11(2):185-8. doi: 10.1038/sj.ejhg.5200934.
Approximately 80% of the hereditary hearing loss is nonsyndromic. Isolated deafness is the most genetically heterogeneous trait. We have ascertained 10 individuals from a large consanguineous Tunisian family with congenital profound autosomal recessive deafness. All affected individuals are otherwise healthy. Genotype analysis excluded linkage to known recessive deafness loci in this family. Following a genome wide screening, a linkage was detected only with locus D1S206 on chromosome 1, thereby defining a novel deafness locus, DFNB32. In order to confirm linkage and for fine mapping the genetic interval, 12 individuals belonging to this family were added and 19 microsatellite markers were tested. A maximum two-point lodscore of 4.96 was obtained at a new polymorphic marker D1S21401. Haplotype analysis defined a 16 Mb critical region between D1S2868 and afmb014zb9. The interval of DFNB32 locus overlap with DFNA37 locus and the Marshall and Stickler syndromes locus. The entire coding region of COL11A1, responsible of the later syndromes, was screened and no mutation was observed. Towards the identification of the DFNB32 gene, a search on the Human Cochlear cDNA Library and EST Database was done. The genes corresponding to the ESTs found in the DFNB32 interval are being screened for deafness-causing mutations.
大约80%的遗传性听力损失是非综合征性的。孤立性耳聋是遗传异质性最高的性状。我们从一个患有先天性重度常染色体隐性耳聋的突尼斯大家族中确定了10名个体。所有受影响的个体在其他方面均健康。基因型分析排除了该家族与已知隐性耳聋位点的连锁关系。经过全基因组筛查，仅在1号染色体上的D1S206位点检测到连锁，从而确定了一个新的耳聋位点DFNB32。为了确认连锁关系并精细定位遗传区间，又增加了该家族的12名个体，并检测了19个微卫星标记。在一个新的多态性标记D1S21401处获得了最大两点连锁分数4.96。单倍型分析确定了D1S2868和afmb014zb9之间一个16 Mb的关键区域。DFNB32位点的区间与DFNA37位点以及马歇尔综合征和斯蒂克勒综合征位点重叠。对与后两种综合征相关的COL11A1的整个编码区进行了筛查，未观察到突变。为了鉴定DFNB32基因，对人类耳蜗cDNA文库和EST数据库进行了搜索。正在对DFNB32区间中发现的EST对应的基因进行致聋突变筛查。
