Discovery of specific mutations in spinal muscular atrophy patients by next-generation sequencing
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ORIGINAL ARTICLE
Discovery of specific mutations in spinal muscular atrophy patients by next-generation sequencing Yu-lian Fang 1 & Na Li 2,3 & Xiu-fang Zhi 4 & Jie Zheng 4 & Yang Liu 2,3 & Lin-jie Pu 4 & Chun-yu Gu 4 & Jian-bo Shu 1,5 & Chun-quan Cai 1,5,6 Received: 24 March 2020 / Accepted: 28 August 2020 # Fondazione Società Italiana di Neurologia 2020
Abstract Spinal muscular atrophy (SMA) is a type of autosomal recessive genetic disease, which seriously threatens the health and lives of children and adolescents. We attempted to find some genes and mutations related to the onset of SMA. Eighty-three whole-blood samples were collected from 28 core families, including 28 probands with clinically suspected SMA (20 SMA patients, 5 nonSMA children, and 3 patients with unknown etiology) and their parents. The multiplex ligation probe amplification (MLPA) was performed for preliminary diagnosis. The high-throughput sequencing technology was used to conduct the whole-exome sequencing analysis. We analyzed the mutations in adjacent genes of SMN1 gene and the unique mutations that only occurred in SMA patients. According to the MLPA results, 20 probands were regarded as experimental group and 5 non-SMA children as control group. A total of 10 mutations were identified in the adjacent genes of SMN1 gene. GUSBP1 g.[69515863G>A], GUSBP1 g.[69515870C>T], and SMA4 g.[69515738C>A] were the top three most frequent sites. SMA4 g.[69515726A>G] and OCLN c.[818G>T] have not been reported in the existing relevant researches. Seventeen point mutations in the DYNC1H1 gene were only recognized in SMA children, and the top two most common mutations were c.[2869-34A>T] and c.[34589A>G]; c.[7473+105C>T] was the splicing mutation that might change the mRNA splicing site. The mutations of SMA4 g.[69515726A>G], OCLN c.[818G>T], DYNC1H1 c.[2869-34A>T], DYNC1H1 c.[345-89A>G], and DYNC1H1 c.[7473+ 105C>T] in the adjacent genes of SMN1 gene and other genes might be related to the onset of SMA. Keywords Spinal muscular atrophy (SMA) . DYNC1H1 . SMA4 . OCLN . High-throughput sequencing
Yu-lian Fang, Na Li, Xiu-fang Zhi and Jie Zheng contributed equally to this work. * Jian-bo Shu [email protected] * Chun-quan Cai [email protected] 1
Institute of Pediatrics, Tianjin Children’s Hospital, 238 Longyan Road, Beichen District, Tianjin 300134, China
2
Department of Neonatology, The Pediatric Clinical College, Tianjin Medical University, Tianjin 300134, China
3
Department of Neonatology, Tianjin Children’s Hospital, Tianjin 300134, China
4
Graduate School, Tianjin Medical University, Tianjin 300070, China
5
Tianjin Key Laboratory of Birth Defects for Prevention and Treatment, Tianjin 300134, China
6
Department of Neurosurgery, Tianjin Children’s Hospital, Tianjin 300134, China
Background Spinal muscular atrophy (SMA) is one of the most common fatal neuromuscular diseases [1], with an incidence of 1/6000 to 1/10000 [2]. The disease is caused by the degeneration of motor neurons in the anterior horn of the spinal cord, resulting in
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