Montagna Giorgia, Teijido Oscar, Eymard-Pierre Eleonore, Muraki Koutarou, Cohen Bruce, Loizzo Annalivia, Grosso Pietro, Tedeschi Gioacchino, Palacín Manuel, Boespflug-Tanguy Odile, Bertini Enrico, Santorelli Filippo M, Estévez Raúl
Molecular Medicine, IRCCS-Bambino Gesù Children's Hospital, Rome, Italy.
Hum Mutat. 2006 Mar;27(3):292. doi: 10.1002/humu.9407.
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.
