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首页> 外文期刊>Case Reports in Genetics >The Use of High-Density SNP Array to Map Homozygosity in Consanguineous Families to Efficiently Identify Candidate Genes: Application to Woodhouse-Sakati Syndrome
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The Use of High-Density SNP Array to Map Homozygosity in Consanguineous Families to Efficiently Identify Candidate Genes: Application to Woodhouse-Sakati Syndrome

机译：使用高密度SNP阵列来映射血缘家庭的纯合子，以有效地识别候选基因：在Woodhouse-Sakati综合征中的应用

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Two consanguineous Qatari siblings presented for evaluation: a 17-4/12-year-old male with hypogonadotropic hypogonadism, alopecia, intellectual disability, and microcephaly and his 19-year-old sister with primary amenorrhea, alopecia, and normal cognition. Both required hormone treatment to produce secondary sex characteristics and pubertal development beyond Tanner 1. SNP array analysis of both probands was performed to detect shared regions of homozygosity which may harbor homozygous mutations in a gene causing their common features of abnormal pubertal development, alopecia, and variable cognitive delay. Our patients shared multiple homozygous genomic regions; ten shared regions were >1 Mb in length and constituted 0.99% of the genome.DCAF17, encoding a transmembrane nuclear protein of uncertain function, was the only gene identified in a homozygous region known to cause hypogonadotropic hypogonadism.DCAF17mutations are associated with Woodhouse-Sakati syndrome, a rare disorder characterized by alopecia, hypogonadotropic hypogonadism, sensorineural hearing loss, diabetes mellitus, and extrapyramidal movements. Sequencing of the coding exons and flanking intronic regions ofDCAF17in the proband revealed homozygosity for a previously described founder mutation (c.436delC). TargetedDCAF17sequencing of his affected sibling revealed the same homozygous mutation. This family illustrates the utility of SNP array testing in consanguineous families to efficiently and inexpensively identify regions of genomic homozygosity in which genetic candidates for recessive conditions can be identified.
机译：提出了两个近亲的卡塔尔兄弟姐妹进行评估：一名患有性腺功能低下性腺功能减退，脱发，智力障碍和小头畸形的17-4 / 12岁男性，以及他的具有原发性闭经，脱发和正常认知的19岁姐姐。两者均需要激素治疗以产生继坦纳1以外的继发性特征和青春期发育。对两个先证者进行SNP阵列分析，以检测纯合子的共享区域，这些区域可能在基因中带有纯合突变，导致其青春期发育异常，脱发和脱发的共同特征。可变的认知延迟。我们的患者共有多个纯合基因组区域;共有10个共享区域，其长度> 1 andMb，占基因组的0.99％.DCAF17编码功能不确定的跨膜核蛋白，是在纯合子区域中唯一已知的导致促性腺激素性性腺功能减退症的基因.DCAF17突变与Woodhouse-Sakati相关综合征，一种以脱发，性腺功能低下性腺功能减退，感觉神经性听力减退，糖尿病和锥体外系运动为特征的罕见疾病。先证者中DCAF17的编码外显子和侧翼内含子区域的测序揭示了先前描述的建立者突变（c.436delC）的纯合性。他受影响的同胞的靶向DCAF17测序显示出相同的纯合突变。该家族说明了在近亲家族中SNP阵列测试的实用性，可以有效和廉价地鉴定基因组纯合子区域，在其中可以鉴定出隐性疾病的遗传候选物。

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