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

Abstract 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.