In human, genetic disorders of the nails are very rare and occur in both isolated and syndromic form. In syndromic forms, anomalies in other ectodermal appendages and/or skeletal deformities are associated with nail disorders. Over the past few years several, different types of human nail disorders have been characterized at clinical and molecular levels. In few cases of nail disorders, causative genes have been identified. In the study presented in the dissertation, eight Pakistani families (A-H) representing isolated form of nail dysplasia (Families A-F) and syndromic nail disorders (Families G and H) have been characterized both at clinical and molecular levels. Family A showed autosomal recessive isolated congenital fingernail dysplasia. Whole exome sequencing of the family revealed a novel variant c.92G>T (p.Arg31Leu; MAF=0.0001; chr10:70,287,041) in the SLC25A16 (NM__152707.4) gene. Affected individuals in two families, B and C, showed typical phenotypes of hereditary leukonychia. Based on the phenotypes observed the PLCD1 gene was sequenced in all available individuals of both families. Analysis of sequencing data showed a recurrent heterozygous mutation c.625T>C (p.Cys209Arg; MAF=0.00009; chr3: 38,052,933) in family B. In family C analysis of sequencing data did not reveal any mutation in PLCD1 (NM_001130964.1) gene. To ascertain the causative gene, the DNA sample of an affected family member has been submitted for exome sequencing. In two other families (D and E) of isolated nail dysplasia, linkage was established to mapped on chromosome 8q22.3. Subsequent sequencing of the FZD6 (NM_003506.4) gene revealed a homozygous non-sense variant c.1750G>T (p.E584X*; MAF=0.00001; chr8:104,342,091) in family D and a homozygous missense variant c.1266G>A ( p.Gly422Asp; MAF=0.00001; chr8:104,342,091) in family E. In family F the nails of Genetic Analysis of Human Hereditary Nail Dysplasia in Pakistani Families the affected individuals were thick and hard with deformed nail bed. After failing to establish linkage to the known genes in the family, DNA samples were used for SNP microarray genotyping. This identified four homozygous regions. To identify a causative gene in the linked regions, DNA sample of an affected individual has been submitted to exome sequencing. In family G, affected individuals displayed typical phenotypes of pure hair and nail ectodermal dysplasia. All affected individuals of the family showed homozygosity with several markers related to HOXC13 (NM_017410.3) gene at chromosome 12p11.1- q21.1. Sequence analysis of HOXC13 revealed a novel homozygous missense mutation c.929A>C (p.Asn310Thr; chr12: 54,338,976). Family H segregated autosomal recessive form of primary hypertrophic osteoarthropathy. Homozygosity mapping, based on whole genome SNP genotyping, lead to the identification of 7.05 Mb homozygous region at chromosome 4q34.1-q34.3. The HPGD (NM_000860.6) gene, located in the homozygous region, was sequenced which detected a homozygous missense variant c.577T>C (p.S193P; chr4: 175,414,387) in all affected family members. The study presented here involves the clinical and genetic analysis of eight families collected from different remote areas of Pakistan. Six of them were characterized by isolated congenital nail dysplasia while two others with syndromic nail disorders. In these families mutation analysis of SLC25A16, PLCD1, FZD6, HOXC13 and HPGD genes revealed some novel and recurrent mutations. In addition, failure to establish linkage to known genes in two families (C and F) directed the existence of undiscovered genes in the human genome triggering nail dysplasia phenotypes.