title: A novel homozygous MCOLN1 double mutant allele leading to TRP channel domain ablation underlies Mucolipidosis IV in an Italian Child.
abstract: Mucolipidosis type IV (MLIV) is a very rare disorder of late endosome/lysosome transport, characterized by neurodevelopmental abnormalities and progressive visual impairment owing to corneal clouding and retinal dystrophy. Greater than 70 % of MLIV patients are of Ashkenazi Jewish ancestry. Here we report a novel MCOLN1double mutant allele [c.395_397delCTG;c.468_474dupTTGGACC] which introduces a premature stop codon [p.Ala132del; p.Asn159LeufsX27] leading to almost complete abrogation of the region coding mucolipin-1, a member of the transient receptor potential (TRP) cation channel family. The genomic lesion was identified in homozygous state, in a non-Jewish Italian MLIV patient, who also presented abnormal serum gastrin levels. Conventional and advanced MRI sequences, including diffusion tensor imaging and tractography, were used for the assessment of white matter involvement in the patient.
authors.affiliation: UO Neuropsichiatria Istituto Giannina Gaslini, Genoa, Italy.
authors.forename: Marisol
authors.initials: M
authors.lastname: Mirabelli-Badenier
authors.forename: Mariasavina
authors.initials: M
authors.lastname: Severino
authors.forename: Barbara
authors.initials: B
authors.lastname: Tappino
authors.forename: Domenico
authors.initials: D
authors.lastname: Tortora
authors.forename: Francesca
authors.initials: F
authors.lastname: Camia
authors.forename: Clelia
authors.initials: C
authors.lastname: Zanaboni
authors.forename: Fabia
authors.initials: F
authors.lastname: Brera
authors.forename: Enrico
authors.initials: E
authors.lastname: Priolo
authors.forename: Andrea
authors.initials: A
authors.lastname: Rossi
authors.forename: Roberta
authors.initials: R
authors.lastname: Biancheri
authors.forename: Maja
authors.initials: M
authors.lastname: Di Rocco
authors.forename: Mirella
authors.initials: M
authors.lastname: Filocamo
mesh_terms: D000483:Alleles; D002675:Child, Preschool; D006720:Homozygote; D006801:Humans; D007558:Italy; D008297:Male; D009081:Mucolipidoses / Q000175:diagnosis / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D050051:Transient Receptor Potential Channels / Q000172:deficiency / Q000235:genetics*; D044465:White People / Q000235:genetics*
chemical_list: C416674:MCOLN1 protein, human; D050051:Transient Receptor Potential Channels