In this study, three Caucasian kindreds with different heterozygous missense variants in ITPR1 are reported. The main clinical manifestation was a slowly progressive gait ataxia with onset after 40 years of age, with chorea in two patients and hand tremor in another one, concordant with manifestations found in SCA15.
The three missense variants identified in ITPR1 were c.1594G>A; p.(Ala532Thr) in Kindred A, c.56C>T; p.(Ala19Val) in Kindred B, and c.256G>A; p.(Ala86Thr) in Kindred C. Every variant was labelled as of unknown significance; however, each one cosegregated with disease and was predicted to be pathogenic by in silico tests.
The three ITPR1 missense variants found in this study exhibited cosegregation with disease, a result that sustains their pathogenicity. Further studies are needed to confirm the role of missense mutations in SCA15.
方法:在本研究中,报告了3个在ITPR1中具有不同杂合错义变异的白种人家族.主要临床表现为缓慢进行性步态共济失调,40岁后发病,两名患者患有舞蹈病,另一名患者患有手震颤,与SCA15中发现的表现一致。
结果:在ITPR1中鉴定出的三个错义变体为:c.1594G>A;p。(Ala532Thr)在家族A中,c.56C>T;p.(Ala19Val)家族B,和c.256G>A;p。(Ala86Thr)在同类C中,每个变体都被标记为未知意义;但是,每一种都与疾病分离,并通过计算机模拟试验预测为致病性。
结论:本研究中发现的三个ITPR1错义变异与疾病共分离,维持其致病性的结果。需要进一步的研究来证实错义突变在SCA15中的作用。