PDF(Pubmed)
Abstract：
Inositol 1,4,5-triphosphate receptor type 1 (ITPR1) is an endoplasmic reticulum-bound intracellular inositol triphosphate receptor involved in the regulation of intracellular calcium. Pathogenic variants in ITPR1 are associated with spinocerebellar ataxia (SCA) types 15/16 and 29 and have recently been implicated in a facial microsomia syndrome. In this report, we present a family with three affected individuals found to have a heterozygous missense c.800C > T (predicted p.Thr267Met) who present clinically with a SCA29-like syndrome. All three individuals presented with varying degrees of ataxia, developmental delay, and apparent intellectual disability, as well as craniofacial involvement-an uncommon finding in patients with SCA29. The variant was identified using clinical exome sequencing and validated with Sanger sequencing. It is presumed to be inherited via parental germline mosaicism. We present our findings to provide additional evidence for germline mosaic inheritance of SCA29, as well as to expand the clinical phenotype of the syndrome.
摘要：
ITPR1是内质网结合的细胞内肌醇三磷酸受体，参与细胞内钙的调节。ITPR1的致病变异与脊髓小脑共济失调（SCA）15/16和29型有关，最近与面部微缩综合征有关。在这份报告中,我们介绍了一个有三个受影响的个体的家庭，发现他们具有杂合错义c.800C>T（预测p.Thr267Met），他们在临床上表现为SCA29样综合征。这三个人都有不同程度的共济失调，发育迟缓,和智力残疾，以及颅面受累；SCA29患者的罕见发现。使用临床全外显子组测序鉴定变体并用Sanger测序验证。推测是通过亲本种系镶嵌遗传的。我们提出了我们的发现，为SCA29的种系马赛克遗传提供了更多证据，并扩大了该综合征的临床表型。
