KIAA0586 is Mutated in Joubert Syndrome.
KIAA0586 is Mutated in Joubert Syndrome.
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DOI：
10.1002/humu.22821
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发表时间：
2015-09
期刊：
影响因子：
3.9
通讯作者：
Doherty D
中科院分区：
文献类型：
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作者：
Bachmann-Gagescu R;Phelps IG;Dempsey JC;Sharma VA;Ishak GE;Boyle EA;Wilson M;Marques Lourenço C;Arslan M;University of Washington Center for Mendelian Genomics;Shendure J;Doherty D
Joubert综合征（JS）是一种隐性神经发育障碍，其特征是独特的中后脑畸形。JS是一组称为纤毛病的疾病的一部分，基于其重叠的表型和与原发性纤毛功能障碍相关的共同的潜在病理生理学。28个基因中的一个的双等位基因突变，所有编码蛋白定位于初级纤毛或基体，可以导致JS。尽管有大量的基因，但目前可以在约62%的JS患者中确定遗传原因。为了鉴定新的JS基因，我们对35名JS患者进行了全外显子组测序，并在一名患者中发现了KIAA 0586中的双等位基因罕见有害变体（RDV），该变体编码纤毛发生所需的中心体蛋白。在一个大型JS队列中进行的靶向下一代测序在另外8个家族中鉴定出双等位基因RDV，估计患病率为2.5%（9/366个JS家族）。所有受影响的个人显示JS表型走向光谱的温和端。
Joubert syndrome (JS) is a recessive neurodevelopmental disorder characterized by a distinctive mid-hindbrain malformation. JS is part of a group of disorders called ciliopathies, based on their overlapping phenotypes and common underlying pathophysiology linked to primary cilium dysfunction. Bi-allelic mutations in one of 28 genes, all encoding proteins localizing to the primary cilium or basal body, can cause JS. Despite this large number of genes, the genetic cause can currently be determined in about 62% of individuals with JS. To identify novel JS genes, we performed whole exome sequencing on 35 individuals with JS and found bi-allelic rare deleterious variants (RDVs) in KIAA0586, encoding a centrosomal protein required for ciliogenesis, in one individual. Targeted next-generation sequencing in a large JS cohort identified bi-allelic RDVs in eight additional families, for an estimated prevalence of 2.5% (9/366 JS families). All affected individuals displayed JS phenotypes toward the mild end of the spectrum.