Mutations in MFSD8/CLN7 are a frequent cause of variant-late infantile neuronal ceroid lipofuscinosis.
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.
Aiello
Chiara
C
Molecular Medicine, Neurology, Radiology, and Pathology, IRCCS-Bambino Gesù Hospital, Rome, Italy.
Terracciano
Alessandra
A
Simonati
Alessandro
A
Discepoli
Giancarlo
G
Cannelli
Natalia
N
Claps
Dianela
D
Crow
Yanick J
YJ
Bianchi
Marzia
M
Kitzmuller
Claudia
C
Longo
Daniela
D
Tavoni
Antonietta
A
Franzoni
Emilio
E
Tessa
Alessandra
A
Veneselli
Edwige
E
Boldrini
Renata
R
Filocamo
Mirella
M
Williams
Ruth E
RE
Bertini
Enrico S
ES
Biancheri
Roberta
R
Carrozzo
Rosalba
R
Mole
Sara E
SE
Santorelli
Filippo M
FM
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
C522398:MFSD8 protein, human; D026901:Membrane Transport Proteins