Abstract:

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.

Key words: spinal muscular atrophy, gene variant, carrier, family genetics, child