Novel Mutation and White Matter Involvement in an Indian Child with Pycnodysostosis

Pycnodysostosis (OMIM # 265800) is an inherited lysosomal disorder due to affection of cathepsin K gene, localised to 1q21. Pycnodysostosis can present with both skeletal and extraskeletal features. The index patient presented with cardinal features of short stature, dental and digital anomalies with history of multiple fractures. He, in addition had an unreported finding of white matter hyperintensity suggesting dysmyelination on neuroimaging. Molecular analysis revealed a homozygous insertion of single nucleotide in exon 5 of the CTSK gene that produces the substitution of phenylalanine instead of leucine at position 160 of protein and a premature termination of protein synthesis due to insertion of a stop codon. This mutation (c.480_481insT), (p.L160fsX173) is a novel frameshift mutation. The index case extends the phenotypic spectrum and the list of previously reported mutations in the CTSK gene.