title: MECP2 mutations are an infrequent cause of mental retardation associated with neurological problems in male patients.
abstract: Mutations in the methyl-CpG-binding protein 2 (MECP2) gene located on Xq28, cause Rett syndrome (RTT) in female patients. Meanwhile, nonmosaic MECP2 mutations unknown in girls have been found in an increasing number of male patients with a normal 46, XY karyotype. They can cause a broad spectrum of neurodevelopmental disorders which often show a combination of mental retardation (MR) with neurological symptoms. We present the results of MECP2 analysis in a group of 72 male patients with an unexplained combination of MR and neurological features, and review the mutational reports published on male patients since the discovery of the MECP2 gene. Analysis included sequencing of exon 1 which thus far was mostly omitted from DNA screening. One pathogenic mutation has been found in a patient with Rett variant, in addition to an unclassified variant and a series of nonpathogenic changes. No changes have been found in exon 1. Criteria for testing of male patients are classic RTT, severe neonatal encephalopathy, and RTT variant which may be clinically underrecognized. Testing can also be considered in males with a combination of unexplained MR and (progressive) neurological manifestations although the yield of MECP2 analysis is probably low in this situation. Based on the literature, MECP2 testing in males with MR only is debatable.
authors.affiliation: Department of Clinical Genetics, University Hospital Maastricht, P.O. Box 5800, 6202 AZ Maastricht, The Netherlands. ute.moog@gen.unimas.nl
authors.forename: Ute
authors.initials: U
authors.lastname: Moog
authors.forename: Kees
authors.initials: K
authors.lastname: Van Roozendaal
authors.forename: Eric
authors.initials: E
authors.lastname: Smeets
authors.forename: Demis
authors.initials: D
authors.lastname: Tserpelis
authors.forename: Koen
authors.initials: K
authors.lastname: Devriendt
authors.forename: Griet Van
authors.initials: GV
authors.lastname: Buggenhout
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Frijns
authors.forename: Connie
authors.initials: C
authors.lastname: Schrander-Stumpel
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis / Q000379:methods; D006801:Humans; D008607:Intellectual Disability / Q000150:complications / Q000235:genetics*; D008297:Male; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009422:Nervous System Diseases / Q000150:complications / Q000235:genetics*; D015518:Rett Syndrome / Q000150:complications / Q000235:genetics
chemical_list: C497392:MECP2 protein, human; D051783:Methyl-CpG-Binding Protein 2