Panthotenate Kinase‐Associated Neurodegeneration Has a Founder Mutation (c.215_216insa) in Indian Agrawal Patients

摘要

The early‐onset classic form of panthotenate kinase‐associated neurodegeneration (PKAN) is a rare genetic disorder of brain iron deposition associated with mutations in the pantothenate kinase 2 gene. Genetic testing was performed in 17 patients with early‐onset classic PKAN and 2 atypical patients identified from a clinic database. Seventeen patients with early‐onset classic disease exhibited pathogenic mutations in the panthotenate kinase 2 (PANK2) gene. One atypical patient had an indeterminate result and the other atypical case was later confirmed to have late‐onset GM1 gangliosidosis. Of the 17, 13 belonged to the Agrawal community, with a common truncating mutation, c.215_216insA, in the homozygous state in all, which is highly suggestive of a founder effect. Of the remaining 4 patients, 2 had novel mutations. PKAN is the third neurological disease after megelencephalic leukoencephalopathy with subcortical cysts and calpainopathy with founder mutations in the Agrawal community.