Vacuolating megalencephalic leukoencephalopathy with subcortical cysts: functional studies of novel variants in MLC1

✍ Scribed by Giorgia Montagna; Oscar Teijido; Eleonore Eymard-Pierre; Koutarou Muraki; Bruce Cohen; Annalivia Loizzo; Pietro Grosso; Gioacchino Tedeschi; Manuel Palacín; Odile Boespflug-Tanguy; Enrico Bertini; Filippo M. Santorelli; Raúl Estévez

• Publisher: John Wiley and Sons
• Year: 2006
• Tongue: English
• Weight: 344 KB
• Volume: 27
• Category: Article
• ISSN: 1059-7794
• DOI: 10.1002/humu.9407

✦ Synopsis

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.