Description of novel variants in consanguineous Pakistani families affected with intellectual disability

다국어 초록 (Multilingual Abstract)

Background Intellectual disability (ID) is a neurodevelopmental condition, affecting 1–3% of the population. Genetic factors play a key role causing the limitation in intellectual functioning and adaptive behavior. The heterogeneity of ID makes it more difficult for genetic and clinical diagnosis. Mapping of variants through next generation DNA sequencing in consanguineous families would help to understand the molecular parthenogenesis of ID.
Objective The aim of this study was to describe the genetic variants of ID in consanguineous Pakistani families.
Methods We analyzed four unrelated consanguineous Pakistani families having an intellectual disability through whole exome sequencing (WES). Data was analyzed using different bioinformatics tools and software.
Results We mapped four novel variants in different ID genes. Each variant is found in different family, co-segregating with a recessive pattern of inheritance. The variants found are; c.1437delG:p.Asn480Thrfs*10, mapped in FKRP, c.2041 C>A:p.Leu681Met in HIRA, c.382 C>T:p.Arg128Cys in BDH1 and c.267+1G>A:p.? identified in TRAPPC6B.
Conclusions These variants help in demonstration of status and molecular basis of intellectual disability in Pakistani population leading to provision of genetic counseling services and a contribution in disease variant database.