PRENATAL EXCLUSION OF IFITM 5 GENE RELATED OSTEOGENESIS IMPERFECTA TYPE V BY MUTATION ANALYSIS; A RARE CASE

Vandana Bansal; Neha Singh; Vasundhara S. Chennuri

Volume : VII, Issue : IV, April - 2018

PRENATAL EXCLUSION OF IFITM 5 GENE RELATED OSTEOGENESIS IMPERFECTA TYPE V BY MUTATION ANALYSIS; A RARE CASE

Vandana Bansal, Neha Singh, Vasundhara S. Chennuri

Abstract :

This case presents an approach to genetic counselling and prenatal diagnosis for a very rare subtype of osteogenesis imperfecta (type V) along with challenges in identification of molecular aetiology and prenatal exclusion of genetic disease with genetic heterogeneity.A 24–year–old, primigravid woman was referred for genetic counselling in the first trimester for husband and his first–degree relatives manifesting features of osteogenesis imperfecta (OI). The husband had multiple fractures since childhood and was wheel chair bound. On pedigree analysis, the mode of inheritance noted in the family was autosomal dominant. Clinical exome covering 6400 genes was performed for the husband which identified heterozygosity for known pathogenic mutation c.–14C>T in IFITM5 gene (OI type V) and variants of uncertain significance (likely pathogenic) c.1870C>T (p. P624S) and c.2330G>A (p. R777H) gene in COL1A2 gene (OI type I). Chorionic villous sampling was done at 13 weeks of gestation. Foetus was heterozygous for the two variants of COL1A2 gene but negative for pathogenic variant in IFITM5 gene. Extended family analysis linked the IFITM5 allele to disease whereas COL1A2 variants were also present in a clinically un–affected paternal aunt suggesting them as possibly benign variants. After mutation analysis of unaffected and affected relatives of husband, it was concluded that variants of COL1A2 gene seen in the fetus, are unlikely to affect foetus from OI as they did not cause disease in the unaffected relative. Pregnancy was continued till term. All antenatal ultrasound findings were normal. She delivered a healthy male child at term. Postnatal course of baby was uneventful with a normal infantogram.This case report highlights the importance of proper genetic evaluation of proband and extended family members by molecular diagnosis and multidisciplinary approach while dealing with such rare genetic disorder for prenatal diagnosis in fetus to improve perinatal outcome by exclusion of disease. < clear="all" style="page–eak–before:always; mso–eak–type:section–eak" />