Delafontaine Hospital Center, Department of Neurology, Saint-Denis, F93200, France.
Department of Toxicology and Genopathies, UF Neurobiology, CHU Lille, Lille, F-59000, France.
BMC Neurol. 2024 Sep 17;24(1):348. doi: 10.1186/s12883-024-03846-2.
Spinocerebellar ataxia type 1, is a rare neurodegenerative disorder with autosomal dominant inheritance belonging to the polyglutamine diseases. The diagnosis of this disease requires genetic testing that may also include the search for CAT interruption of the CAG repeat tract.
One 23-years-old patient suffers from a severe ataxia, with early-onset and rapid progression of the disease. His father might have been affected, but no molecular confirmation has been performed. The genetic results were negative for the Friedreich's ataxia, spinocerebellar ataxia type 2, 3, 6, 7 and 17. The numbers of CAG repeats in the ATXN1 gene was assessed by fluorescent PCR, tripled-primed PCR and enzymatic digestion for the search of sequence interruption in the CAG repeats. The patient carried one pathogenic allele of 61 CAG and one intermediate allele of 37 CAG in the ATXN1 gene. Both alleles were uninterrupted.
We report a rare case of spinocerebellar ataxia type 1 with an intermediate allele and a large SCA1 expansion. The determination of the absence of CAT interruption brought crucial information concerning this molecular diagnosis, the prediction of the disease and had practical consequences for genetic counseling.
脊髓小脑共济失调 1 型是一种罕见的常染色体显性遗传性神经退行性疾病，属于多聚谷氨酰胺疾病。这种疾病的诊断需要基因检测，可能还包括寻找 CAT 中断 CAG 重复序列。
一位 23 岁的患者患有严重的共济失调，疾病早期发病且快速进展。他的父亲可能受到了影响，但没有进行分子确认。基因检测结果排除了弗里德里希共济失调、脊髓小脑共济失调 2、3、6、7 和 17 型。通过荧光 PCR、三引物 PCR 和酶消化技术评估 ATXN1 基因中的 CAG 重复次数，以寻找 CAG 重复序列中的序列中断。患者的 ATXN1 基因携带一个致病性 61 个 CAG 重复的等位基因和一个中间性 37 个 CAG 重复的等位基因。两个等位基因均未中断。
我们报告了一例罕见的脊髓小脑共济失调 1 型病例，存在中间性等位基因和较大的 SCA1 扩展。确定不存在 CAT 中断提供了有关该分子诊断、疾病预测的关键信息，并对遗传咨询具有实际意义。
