title: Mucolipidosis type IV in a Turkish boy associated with a novel MCOLN1 mutation.
abstract: Mucolipidosis type IV is a rare neurodegenerative lysosomal storage disorder that usually presents during the first year of life with severe mental retardation, delayed motor milestones and corneal opacities. Mucolipidosis IV is caused by mutations in MCOLN1, a gene encoding mucolipin-1 which is responsible for maintaining lysosomal function. The majority of known patients with this disorders are Ashkenazi Jews, and most have a splice IVS3-2 A>G, or a 6.4kb deletion mutation in MCOLN1. Here, we present a Turkish patient who, in addition to the typical neurological and visceral characteristics of mucolipidosis type IV, also demonstrates defects in the posterior limb of internal capsule by MRI, micrognathia and clinodactyly of the fifth fingers. Direct sequencing of his DNA revealed a homozygous c.1364C>T (S456L) mutation in MCOLN1, which was heterozygous in both consanguineous parents. This mutation, like several previously described, changes the protein sequence in the channel pore domain of the protein. Serine 456 is conserved in mucolipin proteins throughout evolution, therefore the mutation is considered as causative for the severe phenotype of this patient.
authors.affiliation: Istanbul University, Cerrahpaşa Medical Faculty, Department of Pediatric Genetics, Istanbul, Turkey. beyhan@istanbul.edu.tr
authors.forename: Beyhan
authors.initials: B
authors.lastname: Tüysüz
authors.forename: Ehud
authors.initials: E
authors.lastname: Goldin
authors.forename: Bariş
authors.initials: B
authors.lastname: Metin
authors.forename: Bariş
authors.initials: B
authors.lastname: Korkmaz
authors.forename: Cengiz
authors.initials: C
authors.lastname: Yalçinkaya
mesh_terms: D002648:Child; D003337:Corpus Callosum / Q000473:pathology; D020022:Genetic Predisposition to Disease; D006801:Humans; D020772:Internal Capsule / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D008844:Micrognathism / Q000473:pathology; D009081:Mucolipidoses / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D010641:Phenotype; D017354:Point Mutation / Q000235:genetics*; D050053:TRPM Cation Channels / Q000235:genetics*; D050051:Transient Receptor Potential Channels; D014421:Turkey
chemical_list: C416674:MCOLN1 protein, human; D050053:TRPM Cation Channels; D050051:Transient Receptor Potential Channels