Project Title: Identification and functional studies of genetic variants causing neurodevelopmental disorders in the Pakistani population
Summary: Neurodevelopmental disorders (NDDs) are a group of clinically and genetically heterogeneous disorders, including primary microcephaly, autism spectrum disorder, intellectual disability, developmental delay, cerebral palsy, and other congenital neural anomalies. They are associated with a broad range of symptoms, such as deficits in language, behavioural and other motor functions. Exact incidence in Pakistan is not determined, as yet, however, it is expected to be on the higher side because of high rate of cousin marriages; around 70% of the local population is practicing such unions, making it one of the most inbred populations in the world. Consanguinity increases the probability of a rare recessive disease variant to manifest in offspring in homozygous state leading to an abnormal phenotype. There is no cure available for NDDs. The only option, therefore, is to prevent further affected births in the population by genetic counseling, carrier screening and prenatal diagnosis. Identification of the underlying mutations is the first step towards any disease prevention program.
Consanguineous families with neurodevelopmental disorder will be identified and blood samples will be collected to extract DNA. To identify gene/variants causing NDD, the samples being genotyped using Illumina Global Screening Array, which scores around 0.7 million single nucleotide polymorphisms tag most of the common variation in the human population. Candidate gene variants will be subjected to functional studies.