title: Phenotypic and genotypic variability in four males with MECP2 gene sequence aberrations including a novel deletion.
abstract: The MECP2 gene mutations cause Rett syndrome (RTT) (OMIM: 312750), an X-linked dominant disorder primarily affecting girls. Until RTT was considered lethal in males, although now approximately 60 cases have been reported. Males with MECP2 mutations present with a broad spectrum of phenotypes ranging from neonatal encephalopathy to nonsyndromic mental retardation (MR). Four boys (aged, 3-11 y) were evaluated for MR. Patient 1 had autistic features. Patients 2 and 3 were brothers both presenting with psychomotor delay. Patient 4 showed dysmorphic features and behavioral problems reminiscent of FXS. All patients had a normal 46, XY karyotype and three were tested for FXS with negative results. MECP2 gene analysis of exons 3 and 4 was performed using methods based on the PCR, including Enzymatic Cleavage Mismatched Analysis (ECMA) and direct sequencing. Patient 1 presented somatic mosaicism for the classic RTT p.R106W mutation and patient 4 carried the p.T203M polymorphism. Analysis of the mothers in both cases revealed normal DNA sequences. Patients 2 and 3 had a novel deletion (c.1140del86) inherited from their unaffected mother. MECP2 gene mutations may be considered a rare cause of MR in males although great phenotypic variation hinders genotype-phenotype correlation.
authors.affiliation: Department of Medical Genetics, University of Athens School of Medicine, Choremio Research Laboratory, Aghia Sophia Children's Hospital, Athens 11527, Greece.
authors.forename: Stavroula
authors.initials: S
authors.lastname: Psoni
authors.forename: Christalena
authors.initials: C
authors.lastname: Sofocleous
authors.forename: Joanne
authors.initials: J
authors.lastname: Traeger-Synodinos
authors.forename: Sophia
authors.initials: S
authors.lastname: Kitsiou-Tzeli
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Kanavakis
authors.forename: Helen
authors.initials: H
authors.lastname: Fryssira-Kanioura
mesh_terms: D001321:Autistic Disorder / Q000235:genetics; D002648:Child; D002653:Child Behavior Disorders / Q000235:genetics; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005091:Exons; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics; D007621:Karyotyping; D008297:Male; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics*; D009030:Mosaicism; D010375:Pedigree; D010641:Phenotype; D017354:Point Mutation; D011596:Psychomotor Disorders / Q000235:genetics; D012189:Retrospective Studies; D015518:Rett Syndrome / Q000175:diagnosis / Q000235:genetics* / Q000523:psychology; D017384:Sequence Deletion; D012720:Severity of Illness Index
chemical_list: C497392:MECP2 protein, human; D051783:Methyl-CpG-Binding Protein 2