Introduction Woolly hair (WH) is a rare hereditary hair shaft anomaly, characterized by tightly curled hair. 1 WH is occasionally found to be associated with paucity of scalp and body hair. It may be partial or generalized, which often exhibits light pigmentation and increased hair shaft fragility. 1 WH is a heterogeneous trait that can be manifested as part of a genetic syndrome, such as Naxos disease (MIM 601214) or Carvajal syndrome (MIM 605676) that are characterized by cardiomyopathy with palmoplantar keratoderma and WH. Mutations in the plakoglobin (PKG; MIM 173325) and desmoplakin (DSP; MIM 125647) genes have been reported to cause the Naxos disease and the Carvajal syndrome, respectively. 2,3 Furthermore, a homozygous deletion mutation (c.1841delG) in desmocollin-2 (DSC2; MIM 125645) gene has been reported to be associated with cardiomyopathy and mild palmoplantar keratoderma in association with WH phenotype. 4 The plakoglobin, desmoplakin and desmocollin-2 are family members of desmosomal proteins that function as cell-cell adhesion junction, and are expressed in skin, heart and hair. 5 Nonsyndromic WH is inherited in either autosomal dominant (ADWH; MIM 194300) or autosomal recessive (ARWH; MIM 278150) manner. Hypotrichosis is characterized by sparse hair on scalp and body, sparse or no hair on eyebrow and eyelashes. Mutations in the LPAR6 (MIM 609239) and LIPH (MIM 607365) genes have been reported to cause autosomal recessive WH/hypotrichosis phenotype in various families. 6,7 The LPAR6 and LIPH genes have been shown to have a common signalling pathway and are involved in hair growth in humans. 8 The LPAR6 gene encodes lysophosphatidic acid receptor 6 (LPAR6), whereas, the LIPH codes for lipase H (or a membrane-associated phosphatidic acid-selective phospholipase A1α [mPA-PLA1α]) that produce 2-acyl lysophosphatidic acid (LPA). 8,9 LPA plays an important role in various biological functions and is a ligand of LPAR6. 8,9 The protein products of LPAR6 and LIPH gene are abundantly expressed in the inner root sheath (IRS) of the hair follicle. The LAH2 locus for autosomal recessive hypotrichosis harbouring the LIPH gene has been mapped on chromosome 3q27.3. 10 This locus overlaps with an alopecia mental retardation syndrome (APMR1) locus on chromosome 3q26.33-q27.3. 11 Here we report a large consanguineous Pakistani family suffering from generalized woolly hair with varying degrees of progressive hypotrichosis. The family was collected from Larkana, Sindh. The family contained multiple consanguineous marriages and disease was segregating in an autosomal recessive manner. Pakistan is inhabited by more than 12 linguistically and genetically diverse ethnic groups with unique socio-cultural norms. 12 In Pakistani population ~60% of marriages are described to be 1060 J Pak Med Assoc Identification of LIPH gene mutation in a consanguineous family segregating the woolly hair/hypotrichosis phenotype Sayed Hajan Shah, 1 Aiysha Abid, 2 Saba Shahid, 3 Shagufta Khaliq 4 Centre for Human Genetics and Molecular Medicine, Sindh Institute of Urology and Transplantation, Karachi, 1-3 Department of Human Genetics, University of Health Sciences, Lahore, 4 Pakistan. Abstract Objective: To identify the disease causing gene in a four generation consanguineous family in which eleven family members were suffering from Woolly hair/hypotrichosis phenotype. Methods: Linkage analysis was carried out to identify the disease-causing gene in this family. Genomic DNA of all the available family members was genotyped for the microsatellite markers for all the known woolly hair/hypotrichosis loci. Automated DNA sequencing of the candidate gene was performed to identify the disease- causing mutation. Results: By using homozygosity linkage analysis we have mapped the family on chromosome 3q27.3 with a two point LOD score of 4.04. Mutation screening of the LIPH gene revealed a homozygous c.659_660delTA deletion mutation segregating with the disease phenotype. Conclusion: The results indicate that the c.659_660delTA mutation in the LIPH gene cause autosomal recessive WH/hypotrichosis phenotype in this family. This mutation has been reported in several Pakistani and Guyanese families suggesting a founder mutation in the LIPH gene in Indo-Pak sub-continent. Keywords: Woolly, Hair, Hypotrichosis, LIPH, Pakistan (JPMA 61: 1060; 2011). Original Article