High-throughput screening reveals novel mutations in spinal muscular atrophy patients
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RESEARCH
Open Access
High-throughput screening reveals novel mutations in spinal muscular atrophy patients Ruiping Zhang1†, Chunyu Gu2†, Linjie Pu2†, Yingtao Meng3, Jianbo Shu3,4* and Chunquan Cai3,4,5*
Abstract Background: Spinal muscular atrophy (SMA) is an autosomal recessive hereditary disease associated with severe muscle atrophy and weakness in the limbs and trunk. The discovery of mutated genes is helpful in diagnosis and treatment for SMA. Methods: Eighty-three whole blood samples were collected from 28 core families of clinically suspected SMA, and multiplex ligation probe amplification (MLPA) was performed. Afterwards, the complete gene sequence of SMN1 gene was detected. Furthermore, 20 SMA patients were selected from the 28 probands, and 5 non SMA children as controls. The Life Technologies SOLiD™ technology with mate-pair chemistry was utilized to conduct the whole exome high-throughput sequencing. Results: Twenty-two probands were SMA patients, 3 probands carriers, and 3 probands normal individuals. Moreover, 2 parents from 2 SMA families were with 3 SMN1 exon7 copies. Six SMN1 single nucleotide variants (SNVs) were identified in the 83 samples, and c.[84C > T], c.[271C > T], c.[−39A > G] and g.[70240639G > C] were novel. Compared with control group, 9102 mutation were selected out in SMA patients. SPTA1 mutation c.[−41_40insCTCT], FUT5 SNV c.[1001A > G], and MCCC2 SNV c.[−117A > G] were the 3 most frequent mutations in SMA group (95, 85 and 75%, respectively). Conclusions: We identified some mutations in both SMN1 and other genes, and c.[271C > T], c.[−41_-40insCTCT], c.[1001A > G] and c.[−117A > G] might be associated with the onset of SMA. Keywords: Spinal muscular atrophy (SMA), High-throughput sequencing, SMN1, Onset
Background Spinal muscular atrophy (SMA) is an autosomal recessive hereditary disease characterized by degeneration of spinal cord motor neurons, atrophy of skeletal muscles, and generalized weakness [1]. It affects 1 in 10,000 live births, and often leads to early death [2]. SMA manifests over a wide range of severity, affecting infants through adults. According to the onset time and severity of the disease, SMA is * Correspondence: [email protected]; [email protected] † Ruiping Zhang, Chunyu Gu and Linjie Pu contributed equally to this work. 3 Tianjin Pediatric Research Institute, Tianjin Children’s Hospital, 238 Longyan Road, Beichen District, Tianjin 300134, China Full list of author information is available at the end of the article
divided into 4 types (SMA1, SMA2, SMA3 and SMA4), and SMA 1, with onset before age 6 months; SMA 2, with onset between age 6 and 18 months; SMA 3, with onset in childhood after age 12 months; and SMA 4, with adult onset [3]. Nusinersen (trade name: Spinraza) is the only approved drug to treat spinal muscular atrophy, which is administered directly to the central nervous system using an intrathecal injection [4], but it’s mandatory to have a specific diagnosis in quick time. The genetic profile is essential for the quick and accurate di
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