Mosaicism in ATP1A3-related disorders: not just a theoretical risk
详细信息 查看全文
- 作者：Marie Hully ; Juliette Ropars ; Laurence Hubert ; Nathalie Boddaert…
- 关键词：ATP1A3 ; Mosaicism ; Alternating hemiplegia of childhood (AHC) ; Rapid onset dystonia parkinsonism (RDP) ; Genetic counseling
- 刊名：neurogenetics
- 出版年：2017
- 出版时间：January 2017
- 年：2017
- 卷：18
- 期：1
- 页码：23-28
- 全文大小：
- 刊物类别：Biomedical and Life Sciences
- 刊物主题：Neurosciences; Human Genetics; Molecular Medicine;
- 出版者：Springer Berlin Heidelberg
- ISSN：1364-6753
- 卷排序：18
文摘
Mutations in ATP1A3 are involved in a large spectrum of neurological disorders, including rapid onset dystonia parkinsonism (RDP), alternating hemiplegia of childhood (AHC), and cerebellar ataxia, pes cavus, optic atrophy, and sensorineural hearing loss (CAPOS), with recent descriptions of overlapping phenotypes. In AHC, a few familial cases of autosomal dominant inheritance have been reported, along with cases of de novo sporadic mutations. In contrast, autosomal dominant inheritance has frequently been associated with RDP and CAPOS. Here, we report on two unrelated sets of full siblings with ATP1A3 mutations, (c.2116G>A) p. Gly706Arg in the first family, and (c.2266C>T) p. Arg756Cys in the second family, presenting with familial recurrence of the disease. Both families displayed parental germline mosaicism. In the first family, the brother and sister presented with severe intellectual deficiency, early onset pharmacoresistant epilepsy, ataxia, and autistic features. In the second family, both sisters demonstrated severe encephalopathy with ataxia and dystonia following a regression episode during a febrile episode during infancy. To our knowledge, mosaicism has not previously been reported in ATP1A3-related disorders. This report, therefore, provides evidence that germline mosaicism for ATP1A3 mutations is a likely explanation for familial recurrence and should be considered during recurrence risk counseling for families of children with ATP1A3-related disorders.