Detection of male 2+0 and 1+0 carriers for spinal muscular atrophy by digital PCR

Spinal muscular atrophy (SMA) is an autosomal recessive disease with a high carrier frequency. While current screening methods can identify 1+0 carriers, detecting 2+0 genotypes remains challenging, highlighting the need for additional research. Herein, we applied Digital Polymerase Chain Reaction (dPCR) to develop a novel approach for the detection of male carriers (DMC), especially for those with a 2+0 genotype. The clinical utility of DMC was evaluated in 39 semen samples. Multiple ligation-dependent probe amplification (MLPA) and pedigree analysis were performed on genomic DNA from 111 males and their family members. DMC identified 1+1, 2+1, and 1+0 genotypes in 21, 1, and 8 subjects. Importantly, seven men were identified as 2+0 carriers, while two men were excluded from the 2+0 carrier status. The results of DMC were consistent with those of MLPA and pedigree analysis. DMC provides an inexpensive and accurate method for determining the 2+0 and 1+0 genotypes.

Automated summary

Researchers developed a novel method using dPCR to detect male carriers with a 2+0 genotype of SMA. The clinical utility of this method was evaluated in 39 semen samples, identifying 7 2+0 carriers. This method provides a cost-effective and accurate approach for determining 2+0 genotypes.