Mendelian disorders are caused by alterations in single gene with minimal influence from environment. The large effect size of these variants has always provided important insights into functional annotation of the genome. This knowledge is also instrumental for making important reproductive decisions and therapeutic intervention. Mendelian disorders are globally rare but are observed three folds more frequently in inbred/consanguineous populations. Pakistani population with high rates of consanguinity (>76%) coupled with large family size offers a rich resource for genetic studies of inherited disorders. In this study, eleven families segregating three different diseases Microcephaly, Epilepsy and Ciliopathies analysed using cutting edge technologies. Autosomal recessive primary microcephaly is a neurodevelopmental disorder characterised by congenital reduction in head circumference by >3SD from age and gender appropriate mean. Its incidence varies widely from one in million to one in 10,000; the latter pertaining to northern Pakistani population. To date, seventeen different causative genes have been reported. In this study, genetic analysis of seven families revealed one known and two novel mutations in already reported MCPH genes. Epilepsy is a heterogeneous group of neurological disorders characterized by chronic disposition to recurrent unprovoked seizures. A seizure, by definition, is an episode of abnormal, hypersynchronous activity in a neuronal population of brain that causes sudden involuntary change in behaviour, sensory perception and/or motor activity. Herein, two families were investigated through gene panel sequencing to reveal a reported and a novel mutation underlying epileptic seizures. The third category, ciliopathies, is a group of disorders caused by dysregulation of cilia related functions. Cilia are microtubule based cylindrical projections present on nearly all types of eukaryotic cells and mediate signal transduction of crucial developmental pathways. This study investigated two families, one with clinical diagnosis of a ciliopathy (Joubert Syndrome), while another family, initially undiagnosed, was successfully diagnosed as Nephronophthisis employing advanced genetic analysis. The findings of this study not only expand the mutation spectra, but through detailed clinical characterisation, highlight the diversity of its phenotype too. The knowledge will provide better insights in to disease mechanism and facilitate development of preventive and therapeutic interventions.