CHRNG gene mutations found by whole exome sequencing are related to recurrent pregnancy loss

Abstract

Introduction: Lethal multiple pterygium syndrome (LMPS) is a very rare genetic syndrome that is usually lethal in the second or third trimester of pregnancy. The prevalence of this syndrome is about <1 in 100,000 and homozygous or compound heterozygous mutations of different genes encoding subunits of the acetylcholine receptor will result in and Recurrent pregnancy loss. Materials and methods: Present study involves two couples referred with three and four recurrent miscarriages, respectively. To find out the cause of recurrent miscarriage in these couples, pathological, immunological and hormonal tests were requested for the mother and high-resolution giemsa banding karyotypes were requested for the father and mother. Additionally, the product of abortion from aborted fetus sampling was used for array CGH and whole-exome sequencing in order to perform mutation analysis in both probands. Results: Based on the results, the first proband has a homozygous likely pathogenic variant (NM005199.5: exon 6: c.518dup: p.Tyr173Ter) in the CHRNG. The second proband has homozygous mutation NM005199: exon7: c.753754del: p.P251fs in CHRNG gene as a novel pathogenic mutation of the CHRNG gene, and notably, it is confirmed that both of the above variants are possible risk factors for Lethal type multiple pterygium syndrome and Recurrent pregnancy loss. Conclusion: CHRNG gene mutations variants (NM005199.5: exon 6: c.518dup: p.Tyr173Ter and novel NM005199: exon7: c.753754del: p.P251fs) found by whole exome sequencing are related to Recurrent pregnancy loss. © 2023