Metabolism Unit, Department of Pediatrics, Faculty of Medicine, Hacettepe University, Sıhhiye, Ankara, Turkey.
Pediatr Neurol. 2012 Mar;46(3):172-7. doi: 10.1016/j.pediatrneurol.2011.12.006.
Whole exome sequencing combined with homozygosity mapping comprises a genetic diagnostic tool to identify genetic defects in families with multiple affected members, compatible with presumed autosomal recessively inherited neurometabolic/neurogenetic disease. These tools were applied to a family with two individuals manifesting ataxia, associated with peripheral sensory neuropathy, athetosis, seizures, deafness, and ophthalmoplegia. A novel homozygous missense mutation c.1366C>G (L456V) in C10orf2 (the Twinkle gene) was identified, confirming infantile onset spinocerebellar ataxia in the probands. Signs in infantile onset spinocerebellar ataxia follow a fairly distinct pattern, affecting early development, followed by ataxia and loss of skills. However, this very rare disease was previously reported only in Finland. We suggest that infantile onset spinocerebellar ataxia should be more frequently considered in the differential diagnosis of neurometabolic diseases in childhood. Next-generation sequencing and its use along with homozygosity mapping offer highly promising techniques for molecular diagnosis, especially in small families affected with very rare neurometabolic disorders such as infantile onset spinocerebellar ataxia.
全外显子测序结合纯合子作图是一种遗传诊断工具，可用于鉴定具有多个受影响成员的家族中的遗传缺陷，这些家族的疾病被认为是常染色体隐性遗传的神经代谢/神经遗传疾病。这些工具被应用于一个有两个个体的家庭，这两个个体表现出共济失调，伴有周围感觉神经病、舞蹈手足徐动症、癫痫、耳聋和眼肌麻痹。在 C10orf2（Twinkle 基因）中发现了一个新的纯合错义突变 c.1366C>G (L456V)，这证实了先证者的婴儿期发病的脊髓小脑共济失调。婴儿期发病的脊髓小脑共济失调的症状具有相当明显的模式，影响早期发育，随后出现共济失调和技能丧失。然而，这种非常罕见的疾病以前仅在芬兰有报道。我们建议，在儿童时期神经代谢疾病的鉴别诊断中，应更频繁地考虑婴儿期发病的脊髓小脑共济失调。下一代测序及其与纯合子作图的结合为分子诊断提供了非常有前途的技术，特别是在受非常罕见的神经代谢疾病（如婴儿期发病的脊髓小脑共济失调）影响的小家庭中。
