title: Novel FAM126A mutations in hypomyelination and congenital cataract disease.
abstract: Hypomyelination and congenital cataract (HCC, OMIM #610532) is a rare autosomal recessive disorder due to FAM126A mutations characterized by congenital cataract, progressive neurologic impairment, and myelin deficiency in the central and peripheral nervous system. We have identified two novel mutations in three affected members of two unrelated families. Two sibs harbouring a microdeletion causing a premature stop in the protein showed the classical clinical and neuroradiologic HCC picture. The third patient carrying a missense mutation showed a relatively mild clinical picture without peripheral neuropathy. A residual amount of hyccin protein in primary fibroblasts was demonstrated by functional studies indicating that missense mutations are likely to have less detrimental effects if compared with splice-site mutations or deletions that cause the full-blown HCC phenotype, including peripheral nervous system involvement.
authors.affiliation: Department of Neuroscience, Istituto Giannina Gaslini, Genova, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Traverso
authors.forename: S
authors.initials: S
authors.lastname: Assereto
authors.forename: E
authors.initials: E
authors.lastname: Gazzerro
authors.forename: S
authors.initials: S
authors.lastname: Savasta
authors.forename: E M
authors.initials: EM
authors.lastname: Abdalla
authors.forename: A
authors.initials: A
authors.lastname: Rossi
authors.forename: S
authors.initials: S
authors.lastname: Baldassari
authors.forename: F
authors.initials: F
authors.lastname: Fruscione
authors.forename: G
authors.initials: G
authors.lastname: Ruffinazzi
authors.forename: M R
authors.initials: MR
authors.lastname: Fassad
authors.forename: A
authors.initials: A
authors.lastname: El Beheiry
authors.forename: C
authors.initials: C
authors.lastname: Minetti
authors.forename: F
authors.initials: F
authors.lastname: Zara
authors.forename: R
authors.initials: R
authors.lastname: Biancheri
mesh_terms: D000595:Amino Acid Sequence; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002386:Cataract / Q000151:congenital* / Q000235:genetics* / Q000473:pathology; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics* / Q000473:pathology; D002648:Child; D005260:Female; D006801:Humans; D007223:Infant; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry / Q000235:genetics*; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D016415:Sequence Alignment
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C412048:HYCC1 protein, human
keywords: Cataract; FAM126A gene; Myelination; White matter disorder