LAUSR

BACKGROUND Mucolipidosis III gamma (MLIIIγ) is a rare autosomal recessive disorder characterized by radiographic evidence of mild-to-moderate dysostosis multiplex, progressive joint stiffness and pain, scoliosis, and normal to mildly impaired cognitive development. Cardiac valve involvement and respiratory complications can be significant. MLIIIγ is caused by mutations in the GNPTG, which encodes the γ subunit of the enzyme N-acetylglucosamine-1-phosphotransferase. OBJECTIVE Clinical and genetic study of seven individuals of a consanguineous Pakistani family affected with mucolipidosis phenotype who never pursued medical care. METHODS Genome-wide homozygosity mapping was performed using Affymetrix Human SNP Array 6.0 followed by whole exome and Sanger sequencing. RESULTS The affected individuals showed characteristic clinical features of MLIIIγ. Whole-genome single nucleotide polymorphism genotyping identified a region of homozygosity shared by affected individuals of the family on chromosome 16p13.3. Whole exome sequencing identified a novel 4-bp deletion in the GNPTG segregating in the family in agreement with autosomal recessive pattern. CONCLUSIONS We identified a novel mutation in the GNPTG gene as the underlying cause of MLIIIγ in a Pakistani family. This study supports the role of next-generation sequencing technologies for the molecular diagnosis of rare inherited disorders.