Abstract：
The association of early-onset non-progressive ataxia and miosis is an extremely rare phenotypic entity occasionally reported in the literature. To date, only one family (two siblings and their mother) has benefited from a genetic diagnosis by the identification of a missense heterozygous variant (p.Arg36Cys) in the ITPR1 gene. This gene encodes the inositol 1,4,5-trisphosphate receptor type 1, an intracellular channel that mediates calcium release from the endoplasmic reticulum. Deleterious variants in this gene are known to be associated with two types of spinocerebellar ataxia, SCA15 and SCA29, and with Gillespie syndrome that is associated with ataxia, partial iris hypoplasia, and intellectual disability. In this work, we describe a novel individual carrying a heterozygous missense variant (p.Arg36Pro) at the same position in the N-terminal suppressor domain of ITPR1 as the family previously reported, with the same phenotype associating early-onset non-progressive ataxia and miosis. This second report confirms the implication of ITPR1 in the miosis-ataxia syndrome and therefore broadens the clinical spectrum of the gene. Moreover, the high specificity of the phenotype makes it a recognizable syndrome of genetic origin.
摘要：
早发性非进行性共济失调和瞳孔缩小的关联是文献中偶尔报道的极其罕见的表型实体。迄今为止,通过鉴定错义杂合变体，只有一个家庭（两个兄弟姐妹和他们的母亲）从遗传诊断中受益（p。Arg36Cys)在ITPR1基因中。该基因编码肌醇1,4,5-三磷酸受体1型，这是一种介导内质网钙释放的细胞内通道。已知该基因中的有害变体与两种类型的脊髓小脑共济失调有关，SCA15和SCA29，以及与共济失调相关的Gillespie综合征，部分虹膜发育不全,智力残疾。在这项工作中,我们描述了一个携带杂合错义变体的新个体（p。Arg36Pro）在ITPR1的N末端抑制域中与先前报道的家族相同的位置，与早发性非进行性共济失调和瞳孔缩小相关的表型相同。第二份报告证实了ITPR1在瞳孔缩小-共济失调综合征中的意义，因此扩大了该基因的临床范围。此外，表型的高度特异性使其成为遗传起源的可识别综合征。
