Learning disability also referred as learning disorder or learning difficulty, is a classification characterized mainly by the person’s difficulty in learning and meeting milestones resulting in diverse etiology and patho-physiology. These disorders can make it difficult for a person to learn quickly or in the same manner as someone who is not affected by a learning disability. Usually these disorders are outcome of defects in brain’s ability to receive and process information. People with a learning disability have trouble performing specific skills or completing tasks if left to figure things out by themselves or if taught in conventional ways. Learning disabilities tends to run in families; therefore genetics is believed to be one of the culprits. However, the form of learning disability in parents may appear slightly different in child. A parent who has a writing disorder may have a child with an expressive language disorder which indicates that there may not be a direct link, but a general brain dysfunction may be inherited. The objective of the present study was to identify and characterize genetic mutations responsible for various forms of learning disabilities which will enable many families to get more appropriate diagnostic investigations and the possibility of understanding the cause of disability in the child. In this study a total of 35 inbred families were identified and sampled from various regions of Pakistan suffering with range of learning disabilities including microcephaly (20 families), dyslexia (14 families) and stuttering (1 family). All analyzed families were consanguineous and of Pakistani origin. For the identification of key genetic variants in families suffering with learning disability linkage analysis, genome xx wide SNP analysis and copy number variation were performed, which lead to the characterization of two known mutations c.9557C>G and c.3978G>A and one novel mutation c.6131C>T ASPM gene, mutations in this gene are reported to be the most common cause of microcephaly in Pakistan. An enhancer element was also found in one of the families suffering with mild form of microcephaly. This regulatory region is present 1.2 Mb downstream to ASPM gene which loops back to allow transcription of gene. This enhancer is present in region which is deleted in all affected individuals of the family. This regulatory region is a cis acting element and possesses c.FOS and HeyI elements which are complementary to ASPM promoter. In a genome wide linkage scan of an apparently X linked family suffering with speech disorder, a risk locus for stuttering in Pakistani families at 18p11.32-11.31 is mapped which contains seven candidate genes but no mutation is found so far. In two families with autosomal recessive dyslexia four candidate loci for dyslexia at 2p, 1p, 2q and 4q were also found by Affymetrix SNP 6. The present data extends our knowledge and understanding of the genetic and molecular spectrum of learning disabilities. There are many disorders associated with congenital defects to learn cognitive behaviors and it is necessary to setup a correct diagnosis to avoid unnecessary and ineffective treatment options. Knowledge of specific risk factors may improve our ability to design proper strategies to cope with the impact of disease.