Vacuolating megalencephalic leukoencephalopathy with subcortical cysts: functional studies of novel variants in MLC1.
Nine new unrelated patients presenting vacuolating myelinopathy with subcortical cysts were identified and analyzed for variations in the MLC1 gene. We detected 12 mutations (p.Leu37fs, p.Met80Val, p.Leu83Phe, p.Pro92Ser, p.Ser93Leu, p.Ile108fs, p.Gly130Arg, p.Cys171fs, p.Glu202Lys, p.Ser269Tyr, p.Ala275Asn, and p.Leu310_311insLeu) of which nine were novel. In one patient we did not detect mutations. Using a heterologous system, three new missense variants (p.Glu202Lys, p.Ser269Tyr, and p.Ala275Asn) and a single leucine insertion (p.Leu310insLeu)--lying in a stretch of seven leucines--were functionally assayed by determining total protein levels and mutant protein expression at the plasma membrane. No correlation was observed between mutation, clinical features, and plasma membrane expression of mutant protein.
Molecular Medicine, IRCCS-Bambino Gesù Children's Hospital, Rome, Italy.
Giorgia
G
Montagna
Oscar
O
Teijido
Eleonore
E
Eymard-Pierre
Koutarou
K
Muraki
Bruce
B
Cohen
Annalivia
A
Loizzo
Pietro
P
Grosso
Gioacchino
G
Tedeschi
Manuel
M
Palacín
Odile
O
Boespflug-Tanguy
Enrico
E
Bertini
Filippo M
FM
Santorelli
Raúl
R
Estévez
D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002462:Cell Membrane / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D005260:Female; D005786:Gene Expression Regulation; D014644:Genetic Variation; D020279:Hereditary Central Nervous System Demyelinating Diseases / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D009865:Oocytes / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014981:Xenopus
C425069:MLC1 protein, human; D008565:Membrane Proteins