沙特阿拉伯人群中非综合征性听力损失的遗传基础的综合介绍。
A comprehensive introduction to the genetic basis of non-syndromic hearing loss in the Saudi Arabian population.
机构信息
Department of Genetics, King Faisal Specialist Hospital & Research Centre, PO Box 3354, Riyadh 11211, Saudi Arabia.
出版信息
BMC Med Genet. 2011 Jul 4;12:91. doi: 10.1186/1471-2350-12-91.
BACKGROUND
Hearing loss is a clinically and genetically heterogeneous disorder. Mutations in the DFNB1 locus have been reported to be the most common cause of autosomal recessive non-syndromic hearing loss worldwide. Apart from DFNB1, many other loci and their underlying genes have also been identified and the basis of our study was to provide a comprehensive introduction to the delineation of the molecular basis of non-syndromic hearing loss in the Saudi Arabian population. This was performed by screening DFNB1 and to initiate prioritized linkage analysis or homozygosity mapping for a pilot number of families in which DFNB1 has been excluded.
METHODS
Individuals from 130 families of Saudi Arabian tribal origin diagnosed with an autosomal recessive non-syndromic sensorineural hearing loss were screened for mutations at the DFNB1 locus by direct sequencing. If negative, genome wide linkage analysis or homozygosity mapping were performed using Affymetrix GeneChip® Human Mapping 250K/6.0 Arrays to identify regions containing any known-deafness causing genes that were subsequently sequenced.
RESULTS
Our results strongly indicate that DFNB1 only accounts for 3% of non-syndromic hearing loss in the Saudi Arabian population of ethnic ancestry. Prioritized linkage analysis or homozygosity mapping in five separate families established that their hearing loss was caused by five different known-deafness causing genes thus confirming the genetic heterogeneity of this disorder in the kingdom.
CONCLUSION
The overall results of this study are highly suggestive that underlying molecular basis of autosomal recessive non-syndromic deafness in Saudi Arabia is very genetically heterogeneous. In addition, we report that the preliminary results indicate that there does not seem to be any common or more prevalent loci, genes or mutations in patients with autosomal recessive non-syndromic hearing loss in patients of Saudi Arabian tribal origin.
背景
听力损失是一种临床和遗传上具有异质性的疾病。DFNB1 基因座的突变已被报道为全球常染色体隐性非综合征性听力损失的最常见原因。除了 DFNB1 之外，许多其他基因座及其潜在基因也已被确定，我们的研究基础是全面介绍沙特阿拉伯人群中非综合征性听力损失的分子基础。这是通过筛选 DFNB1 并为已排除 DFNB1 的一小部分家庭启动优先连锁分析或纯合子作图来完成的。
方法
来自 130 个沙特阿拉伯部落家族的个体，这些家族被诊断为常染色体隐性非综合征性感觉神经性听力损失，通过直接测序筛选 DFNB1 基因座的突变。如果为阴性，则使用 Affymetrix GeneChip® Human Mapping 250K/6.0 Arrays 进行全基因组连锁分析或纯合作图，以鉴定包含任何已知致聋基因的区域，随后对这些基因进行测序。
结果
我们的结果强烈表明，DFNB1 仅占沙特阿拉伯种族人群中非综合征性听力损失的 3%。对五个不同家庭的优先连锁分析或纯合作图表明，他们的听力损失是由五个不同的已知致聋基因引起的，从而证实了该疾病在该王国的遗传异质性。
结论
本研究的总体结果高度表明，沙特阿拉伯常染色体隐性非综合征性耳聋的潜在分子基础具有高度遗传异质性。此外，我们报告初步结果表明，沙特阿拉伯部落起源的常染色体隐性非综合征性听力损失患者似乎没有任何常见或更普遍的基因座、基因或突变。
Zotero 插件