Familial study of spinal muscular atrophy carriers with SMN1 (2+0) genotype.

Spinal muscular atrophy (SMA) is a common childhood neuromuscular disease inherited in an autosomal recessive pattern. The majority of SMA patients have a homozygous deletion of survival motor neuron 1 (SMN1) gene. As a special SMA carrier, the (2+0) genotype ofSMN1 poses a great challenge for carrier screening and family genetic counseling. A previous study showed that polymorphisms of g.27134 T>G and g.27706_27707delAT had a predictive effect on (2+0) carriers in the Ashkenazi Jewish population. To further explore whether these two polymorphisms are specific to the Chinese population, the present study recruited 44 family members and 204 controls with knownSMN1copy number. These 44 family members were from nine unrelated SMA families withSMN1 homozygous deletion, and one of the proband parents was suspected to be a (2+0) carrier. Multiplex ligation-dependent probe amplification (MLPA) and short tandem repeat (STR) linkage analyses were used to determine the (2+0) genotype and polymorphism screening. Finally, by analyzing theSMN copies and haplotype from three generations of family members and two generations of multi-child families, ten individuals in nine families were confirmed as (2+0) carriers. Moreover, only one individual with three copies ofSMN1 carried the two polymorphisms of g.27134 T>G and g.27706_27707delAT. Therefore, we provided precise genetic counseling for these SMA families after confirming the (2+0) carriers. The association between the polymorphisms of g.27134T>G and g.27706_27707delAT and Chinese (2+0) carriers might be weak. Hence, it is necessary to find specific polymorphisms in the Chinese population to improve the detection rate of (2+0) carriers.