title: Molecular genetic studies in Indian patients with megalencephalic leukoencephalopathy.
abstract: Mutations in the MLC1 gene cause megalencephalic leukoencephalopathy with subcortical cysts. We sought to identify mutations in the MLC1 gene, to evaluate the genotype-phenotype correlation, and to develop a strategy for diagnosing Indian patients with megalencephalic leukoencephalopathy. Forty patients were enrolled. We developed a rapid restriction fragment length polymorphism method to screen a common mutation, c.135_136insC. Rare and novel mutations were screened by conformation-sensitive gel electrophoresis, followed by sequencing. Three previously reported and two novel mutations were identified in 37 patients. The presence of the c.135_136insC mutation in 29 patients of the Agarwal community suggests a founder effect. The mutation c.959C>A was evident in four patients, and appears to be the second commonest mutation. Genotype could not predict phenotype. We recommend screening for the commonest mutation (c.135_136insC), followed by the next commonest mutation (c.959C>A), and then other rare mutations, using conformation-sensitive gel electrophoresis analysis or direct sequencing.
authors.affiliation: Division of Genetics, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Pallavi
authors.initials: P
authors.lastname: Shukla
authors.forename: Neerja
authors.initials: N
authors.lastname: Gupta
authors.forename: Manju
authors.initials: M
authors.lastname: Ghosh
authors.forename: Suman
authors.initials: S
authors.lastname: Vasisht
authors.forename: Sheffali
authors.initials: S
authors.lastname: Gulati
authors.forename: Prahlad
authors.initials: P
authors.lastname: Balakrishnan
authors.forename: Raju
authors.initials: R
authors.lastname: Sharma
authors.forename: Arun K
authors.initials: AK
authors.lastname: Gupta
authors.forename: Mahesh
authors.initials: M
authors.lastname: Kamate
authors.forename: Veena
authors.initials: V
authors.lastname: Kalra
authors.forename: Madhulika
authors.initials: M
authors.lastname: Kabra
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D003560:Cysts / Q000175:diagnosis* / Q000235:genetics*; D018703:Founder Effect; D005820:Genetic Testing / Q000379:methods; D020279:Hereditary Central Nervous System Demyelinating Diseases / Q000175:diagnosis* / Q000235:genetics*; D006801:Humans; D007194:India; D007223:Infant; D008565:Membrane Proteins / Q000235:genetics; D009154:Mutation / Q000235:genetics; D012150:Polymorphism, Restriction Fragment Length / Q000235:genetics; D044465:White People / Q000235:genetics*
chemical_list: C425069:MLC1 protein, human; D008565:Membrane Proteins