title: CLN6 disease caused by the same mutation originating in Pakistan has varying pathology.
abstract: The neuronal ceroid lipofuscinoses (NCLs), the most common neurodegenerative diseases in children, are characterised by storage of autofluorescent material that has a characteristic ultrastructure. We report two families with variant late infantile NCL, both originating from Pakistan. Probands from both families were homozygous for the same mutation (c.316dupC) but had variable pathology to that currently thought to be typical for CLN6 disease, late infantile variant. The observed pathology of one proband resembled condensed fingerprints, previously described in late infantile CLN7 and CLN8 diseases, and pathology from the second proband was thought to be absent even after repeated skin biopsy, but observed after review. This mutation is the most common NCL mutation in families originating from Pakistan and could be prioritised for testing. Finally, this report contains the first prenatal diagnosis for late infantile CLN6 disease, initially made on the basis of EM and now confirmed by mutation analysis.
authors.affiliation: Department of Molecular Neuroscience, Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK.
authors.forename: Rita
authors.initials: R
authors.lastname: Guerreiro
authors.forename: Jose T
authors.initials: JT
authors.lastname: Bras
authors.forename: Mariana
authors.initials: M
authors.lastname: Vieira
authors.forename: Varun
authors.initials: V
authors.lastname: Warrier
authors.forename: Shakti
authors.initials: S
authors.lastname: Agrawal
authors.forename: Helen
authors.initials: H
authors.lastname: Stewart
authors.forename: Glenn
authors.initials: G
authors.lastname: Anderson
authors.forename: Sara E
authors.initials: SE
authors.lastname: Mole
mesh_terms: D001808:Blood Vessels / Q000473:pathology / Q000648:ultrastructure; D002648:Child; D006801:Humans; D008214:Lymphocytes / Q000473:pathology / Q000648:ultrastructure; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D009472:Neuronal Ceroid-Lipofuscinoses / Q000235:genetics* / Q000473:pathology*; D010154:Pakistan
chemical_list: C447500:CLN6 protein, human; D008565:Membrane Proteins
keywords: Batten; CLN6; NCL; Neuronal ceroid lipofuscinosis; Pathology; Prenatal