title: A novel mutation in a large family causes a unique phenotype of Mucolipidosis IV.
abstract: Mucolipidosis type IV is a rare autosomal recessive lysosomal storage disorder reported among Ashkenazi Jews and to a lesser extent in other ethnic groups. Several mutations have been reported in MCOLN1 which is the only known gene associated with the disorder. Here we report the first Saudi patient with Mucolipidosis type IV from a consanguineous family with two branches having a total of five patients carrying a novel transition mutation, c.1307A>G (p.Y436C) in exon 11. The clinical course of the patient was nonspecific and a lysosomal storage disorder was not highly suspected due to lack of coarse facial features, organomegaly and skeletal findings of dysostosis multiplex. The detailed bioinformatics analysis on the deleterious effects of the mutation is discussed. Emphasis is made on the importance of brain magnetic resonance imaging (MRI) findings and serum gastrin level as key clues to the diagnosis of this often subtle neurodevelopmental disorder.
authors.affiliation: Department of Genetics, King Faisal Specialist Hospital and Research Center, MBC 03, Riyadh 11211, Saudi Arabia.
authors.forename: AlBandary
authors.initials: A
authors.lastname: AlBakheet
authors.forename: Aliya
authors.initials: A
authors.lastname: Qari
authors.forename: Dilek
authors.initials: D
authors.lastname: Colak
authors.forename: Anas
authors.initials: A
authors.lastname: Rasheed
authors.forename: Namik
authors.initials: N
authors.lastname: Kaya
authors.forename: Moeenaldeen
authors.initials: M
authors.lastname: Al-Sayed
mesh_terms: D001921:Brain / Q000473:pathology; D002648:Child; D003241:Consanguinity; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009081:Mucolipidoses / Q000175:diagnosis* / Q000235:genetics*; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D050051:Transient Receptor Potential Channels / Q000235:genetics*
chemical_list: C416674:MCOLN1 protein, human; D050051:Transient Receptor Potential Channels
keywords: DNA; Gastrin; HGMD; Human Gene and Mutation Database; IVS; KFSHRC; King Faisal Specialist Hospital and Research Center; LOD; MCOLN1; ML IV; MRI; Mucolipidosis type IV; Novel p.Y436C; Polyphen; RAC; Research Advisory Council; SIFT; deoxyribonucleic acid; intervening sequence intron; logarithm of odds; magnetic resonance imaging; mucolipin 1 gene; polymorphism phenotyping; sorts intolerant from tolerant