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“1^d+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+1^d”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。

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 "1^d +0" type of compound heterozygous variant of SMN1 gene (1^d: c.22_23insA). The mother had a "1+1^d" 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.