复合杂合变异脊髓性肌萎缩症1例报告
收稿日期: 2021-12-16
网络出版日期: 2022-03-09
基金资助
浙江省“尖兵”“领雁”研发攻关计划项目(2022C03167);浙江省基础公益分析测试项目(LGC21H090004);国家自然科学基金项目(81801490);国家中心自主设计项目-拔尖青年人才培育项目(Q21C0002)
A rare case of children with compound heterozygous variant of spinal muscular atrophy
Received date: 2021-12-16
Online published: 2022-03-09
脊髓性肌萎缩症是一种常染色体隐性遗传病,常规基因诊断方法无法检出隐性遗传病携带者,易造成诊断延误,加重家庭及社会负担。先证者,男性,2月龄,生后哭声低弱、四肢无力,肌电图示脊髓前角细胞病变。采取多重连接探针扩增技术、长片段PCR扩增、连锁分析诊断患儿SMN1基因为“1d+0”型复合杂合变异(1d:c.22_23insA)。家系遗传学分析提示母亲为“1+1d”型、父亲为“2+0”型隐性遗传病携带者,目前此种遗传模式未见报道。随访先证者并予遗传咨询后指导其母顺利生育1名健康女婴。隐性遗传病携带者的存在将增加脊髓性肌萎缩症患儿的漏诊率,排查隐性遗传病携带者有利于疾病早期精准诊断,避免出生缺陷。
姚妹 , 冯艺杰 , 夏雨 , 周栋明 , 金佳宁 , 魏佳 , 崔易沁 , 毛姗姗 . 复合杂合变异脊髓性肌萎缩症1例报告[J]. 临床儿科杂志, 2022 , 40(3) : 212 -217 . DOI: 10.12372/jcp.2022.21e1726
Spinal muscular atrophy (SMA) is an autosomal recessive genetic disease. Conventional genetic testing cannot detect the silent carriers, which can easily lead to the delay of diagnosis and increase the burden of family and society. A 2-month-old male proband was born with a weak crying and weakness of the limbs. The electromyography indicated that there was an anterior horn cell lesion in the spinal cord. The diagnosis and genetic characteristics of the family were confirmed by multiplex ligation-dependent probe amplification, long-fragment PCR amplification and linkage analysis. The result suggested that the child had a "1d +0" type of compound heterozygous variant of SMN1 gene (1d: c.22_23insA). The mother had a "1+1d" genotype and the father was a silent carrier with a "2+0" genotype. This genetic pattern has not been reported so far. A healthy female child was born in this family after following the guidance of genetic counseling. The presence of silent carriers will increase the rate of missed diagnosis in patients with SMA. Screening for silent carriers is conducive to early and accurate diagnosis of the disease and can avoid the birth defects.
Key words: spinal muscular atrophy; gene variant; carrier; family genetics; child
[1] | Hamilton G, Gillingwater TH. Spinal muscular atrophy: going beyond the motor neuron[J]. Trends Mol Med, 2013, 19(1): 40-50. |
[2] | Verhaart IEC, Robertson A, Wilson IJ, et al. Prevalence, incidence and carrier frequency of 5q-linked spinal muscular atrophy - a literature review[J]. Orphanet J Rare Dis, 2017, 12(1): 124. |
[3] | Monani UR, Lorson CL, Parsons DW, et al. A single nucleotide difference that alters splicing patterns distinguishes the SMA gene SMN1 from the copy gene SMN2[J]. Hum Mol Genet, 1999, 8(7): 1177-1183. |
[4] | Wirth B, Garbes L, Riessland M. How genetic modifiers influence the phenotype of spinal muscular atrophy and suggest future therapeutic approaches[J]. Curr Opin Genet Dev, 2013, 23(3): 330-338. |
[5] | Wirth B. An update of the mutation spectrum of the survival motor neuron gene (SMN1) in autosomal recessive spinal muscular atrophy (SMA)[J]. Hum Mutat, 2000, 15(3): 228-237. |
[6] | Ogino S, Wilson RB. Genetic testing and risk assessment for spinal muscular atrophy (SMA)[J]. Hum Genet, 2002, 111(6): 477-500. |
[7] | Butcher S, Smith M, Woodcock IR, et al. False negative carrier screening in spinal muscular atrophy[J]. J Child Neurol, 2020, 35(4): 274-277. |
[8] | Mercuri E, Finkel RS, Muntoni F, et al. Diagnosis and management of spinal muscular atrophy. Part 1: Recommendations for diagnosis, rehabilitation, orthopedic and nutritional care[J]. Neuromuscul Disord, 2018, 28(2): 103-115. |
[9] | Finkel RS, Mercuri E, Meyer OH, et al. Diagnosis and management of spinal muscular atrophy. Part 2: Pulmonary and acute care; medications, supplements and immunizations; other organ systems; and ethics[J]. Neuromuscul Disord, 2018, 28: 197-207. |
[10] | 北京医学会医学遗传学分会, 北京罕见病诊疗与保障学会. 脊髓性肌萎缩症遗传学诊断专家共识[J]. 中华医学杂志, 2020, 100(40): 3130-3140. |
[11] | Finkel RS, Mercuri E, Darras BT, et al. Nusinersen versus sham control in infantile-onset spinal muscular atrophy[J]. N Engl J Med, 2017, 377(18): 1723-1732. |
[12] | Chan SH, Chae JH, Chien YH, et al. Nusinersen in spinal muscular atrophy type 1 from neonates to young adult: 1-year data from three Asia-Pacific regions[J]. J Neurol Neurosurg Psychiatry, 2021, 92(11): 1244-1246. |
[13] | Tsai CH, Jong YJ, Hu CJ, et al. Molecular analysis of SMN, NAIP and P44 genes of SMA patients and their families[J]. J Neurol Sci, 2001, 190(1-2): 35-40. |
[14] | Wang CC, Chang JG, Chen YL, et al. Multi-exon genotyping of SMN gene in spinal muscular atrophy by universal fluorescent PCR and capillary electrophoresis[J]. Electrophoresis, 2010, 31(14): 2396-2404. |
[15] | Alías L, Barceló MJ, Bernal S, et al. Improving detection and genetic counseling in carriers of spinal muscular atrophy with two copies of the SMN1 gene[J]. Clin Genet, 2014, 85(5): 470-475. |
[16] | Ar Rochmah M, Awano H, Awaya T, et al. Spinal muscular atrophy carriers with two SMN1 copies[J]. Brain Dev, 2017, 39(10): 851-860. |
[17] | 曹延延, 程苗苗, 宋昉, 等. 脊髓性肌萎缩症SMN1基因2+0基因型携带者的家系研究[J]. 遗传, 2021, 43(2): 160-168. |
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