Whole exome sequencing provides a diagnosis of spinal muscular atrophy pedigree with SMN1 “2+0” genotype

Abstract Background Spinal muscular atrophy (SMA) is one of the common autosomal recessive neuromuscular disease caused by mutations of the SMN1 gene. As a special SMA carrier, the “2 + 0” genotype of SMN1 poses a great challenge for carrier screening and family genetic counseling. Methods In this study, for the first time, we identified “2 + 0” genotype carriers via trio-based whole exome sequencing (WES) and sequencing based multiple single nucleotide polymorphisms (SNPs) haplotype linkage analysis. Results Combined with the copy number of SMN1 gene in family members, the genetic relationship of SMN1 pathogenic gene transmitted from grandmother to father and then to proband was confirmed. Conclusion Our study suggest that SNPs transmitted through multiple generations in a family could be screened by using WES sequencing to realize linkage analysis. And we determine that the SMN1 genotypes of proband’s father and grandmother are “2 + 0” genotype carriers.