PDF(Pubmed)
Abstract：
KIAA0586 variants have been associated with a wide range of ciliopathies, mainly Joubert syndrome (JS, OMIM #616490) and short-rib thoracic dysplasia syndrome (SRTD, OMIM #616546). However, the hypothesis that this gene is involved with hydrolethalus syndrome (HSL, OMIM #614120) and orofaciodigital syndrome IV (OMIM #258860) has already been raised. Ciliopathies\' clinical features are often overlapped despite differing in phenotype severity. Besides KIAA0586, HYLS1 and KIF7 are also known for being causative of ciliopathies, indicating that all three genes may have similar or converging genomic pathways. Overall, the genotypic and phenotypic spectrum of ciliopathies becomes wider and conflicting while more and more new variants are added to this group of disorders\' molecular pot. In this case report we discuss the first Brazilian individual clinically diagnosed with hydrolethalus syndrome and molecular findings that demonstrate the role of KIAA0586 as a causative gene of a group of genetic disorders. Also, recent reports on individuals with intronic and exonic variants combined leading to ciliopathies support our patient\'s molecular diagnosis. At the same time, we discuss variable expressivity and overlapping features in ciliopathies.
摘要：
KIAA0586变体与广泛的纤毛病有关，主要是Joubert综合征(JS，OMIM＃616490）和短肋骨胸部发育不良综合征（SRTD，OMIM#616546)。然而,该基因与水提道综合征有关的假设(HSL，OMIM＃614120）和口交症IV（OMIM＃258860）已经提出。尽管表型严重程度不同，但纤毛病的临床特征通常重叠。除KIAA0586外，HYLS1和KIF7也因引起纤毛病而闻名，这表明所有三个基因可能具有相似或趋同的基因组途径。总的来说,纤毛病的基因型和表型谱变得更广泛和冲突，而越来越多的新变异体被添加到这一疾病的分子库。在此病例报告中，我们讨论了第一个被临床诊断为患有水提道综合征的巴西个体，以及证明KIAA0586作为一组遗传性疾病的致病基因的分子发现。此外，最近关于内含子和外显子变异导致纤毛病变的个体的报道支持我们患者的分子诊断。同时,我们讨论了纤毛病中的可变表达和重叠特征。
