Molecular-genetic study of SMN1 and SMN2 genes associated with spinal muscular atrophy in individuals with infertility prior to in vitro fertilization

Abstract

Introduction. The rate of infertile couples comprises 17–24 % and tends to increase, with more of them turning to assisted reproductive technologies (ART). In case a required result is achieved, future parents-to-be prepare for birth of a healthy child in the family, but each couple may face a birth of offspring with severe genetic disorders including spinal muscular atrophy (SMA).Aim: to access a carriage rate for SMN1 gene exon 7 deletion associated with SMA and SMN2 gene copy number in married couples planning childbirth using in vitro fertilization (IVF).Materials and Methods. There were enrolled 170 couples (340 subjects) suffering from infertility and referred for IVF in the Sverdlovsk region (SR) of Russia. The search for deletions/duplications in the SMN1 and SMN2 genes was carried out by quantitatively analyzing number of gene copies using the SALSA MLPA Probemix P460 commercial kit (MRC-Holland, the Netherlands). The Hardy–Weinberg ratio was used to calculate estimated rate of homozygous carriers with SMN1 deletions in the next generation.Results. Among 340 patients, a deletion of exon 7 in the SMN1 gene (one copy out of two) was found in 9 individuals (3 males and 6 females) unrelated to marital relations. Thus, only 9 out of 340 examined subjects carry such gene mutation associated with SMA, with total rate of carriage comprised 2.65 % (1/38). Given the number of IVF procedures performed in SR, it may be assumed that the probability for birth of a sick child in such couple comprises at least 1:6410. A number of patients had SMN1 gene duplications – 9 (5.29 %) males and 4 (2.35 %) females baring 3 copies of the SMN1 gene. In addition, the majority of study participants (54 %) turned out to have 3 copies of the SMN2 gene.Conclusion. The rate of SMA carriage in married couples planning a pregnancy with aid of ART corresponds to the general population reaching 1:38 level. It is believed necessary that all couples entering the IVF program should be examined for carriage of SMN1 gene mutations to assess SMA risk in offspring.