title: Mutations in MFSD8/CLN7 are a frequent cause of variant-late infantile neuronal ceroid lipofuscinosis.
abstract: The neuronal ceroid lipofuscinoses (NCL) are a group of genetically heterogeneous neurodegenerative disorders. The recent identification of the MFSD8/CLN7 gene in a variant-late infantile form of NCL (v-LINCL) in affected children from Turkey prompted us to examine the relative frequency of variants in this gene in Italian patients with v-LINCL. We identified nine children harboring 11 different mutations in MFSD8/CLN7. Ten mutations were novel and included three nonsense (p.Arg35Stop, p.Glu381Stop, p.Arg482Stop), four missense (p.Met1Thr, p.Gly52Arg, p.Thr294Lys, p.Pro447Leu), two splice site mutations (c.863+3_4insT, c.863+1G>C), and a 17-bp deletion predicting a frameshift and premature protein truncation (c.627_643del17/p.Met209IlefsX3). The clinical phenotype, which was similar to that of the Turkish v-LINCL cases, was not influenced by type and location of the mutation nor the length of the predicted residual gene product. As well as identifying novel variants in MFSD8/CLN7, this study contributes to a better molecular characterization of Italian NCL cases, and will facilitate medical genetic counseling in such families. The existence of a subset of v-LINCL cases without mutations in any of the known NCL genes suggests further genetic heterogeneity.
authors.affiliation: Molecular Medicine, Neurology, Radiology, and Pathology, IRCCS-Bambino Gesù Hospital, Rome, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Aiello
authors.forename: Alessandra
authors.initials: A
authors.lastname: Terracciano
authors.forename: Alessandro
authors.initials: A
authors.lastname: Simonati
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Discepoli
authors.forename: Natalia
authors.initials: N
authors.lastname: Cannelli
authors.forename: Dianela
authors.initials: D
authors.lastname: Claps
authors.forename: Yanick J
authors.initials: YJ
authors.lastname: Crow
authors.forename: Marzia
authors.initials: M
authors.lastname: Bianchi
authors.forename: Claudia
authors.initials: C
authors.lastname: Kitzmuller
authors.forename: Daniela
authors.initials: D
authors.lastname: Longo
authors.forename: Antonietta
authors.initials: A
authors.lastname: Tavoni
authors.forename: Emilio
authors.initials: E
authors.lastname: Franzoni
authors.forename: Alessandra
authors.initials: A
authors.lastname: Tessa
authors.forename: Edwige
authors.initials: E
authors.lastname: Veneselli
authors.forename: Renata
authors.initials: R
authors.lastname: Boldrini
authors.forename: Mirella
authors.initials: M
authors.lastname: Filocamo
authors.forename: Ruth E
authors.initials: RE
authors.lastname: Williams
authors.forename: Enrico S
authors.initials: ES
authors.lastname: Bertini
authors.forename: Roberta
authors.initials: R
authors.lastname: Biancheri
authors.forename: Rosalba
authors.initials: R
authors.lastname: Carrozzo
authors.forename: Sara E
authors.initials: SE
authors.lastname: Mole
authors.forename: Filippo M
authors.initials: FM
authors.lastname: Santorelli
mesh_terms: D000293:Adolescent; D000595:Amino Acid Sequence; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D006801:Humans; D007558:Italy; D008279:Magnetic Resonance Imaging; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D009472:Neuronal Ceroid-Lipofuscinoses / Q000235:genetics* / Q000473:pathology; D010375:Pedigree; D017386:Sequence Homology, Amino Acid
chemical_list: C522398:MFSD8 protein, human; D026901:Membrane Transport Proteins