title: Characterization of six novel patients with MECP2 duplications due to unbalanced rearrangements of the X chromosome.
abstract: Males with duplication of the Xq28 region, including methyl CpG-binding protein 2 (MECP2), exhibit a characteristic phenotype, including developmental delay, intellectual disability, limited or absent speech, limited or absent ambulation, and recurrent respiratory infections. We report six males with MECP2 duplications identified using array comparative genomic hybridization. The minimal sizes of these duplications range from ∼0.08 to 14.13 Mb, which, to the best of our knowledge, are respectively the smallest and largest minimal size duplications molecularly characterized to date. Adjunct metaphase fluorescence in situ hybridization analysis further classified these duplications as tandem or as products of complex chromosomal rearrangements. Specifically, one complex rearrangement was described as a der(12)t(X;12)(q28;q24.33), which is the first report of a translocation involving MECP2 on Xq and chromosome 12. The other complex rearrangement was described as a rec(X)dup(Xq)inv(X)(p22.32q28)mat. Synthesis of the dysmorphic features identified in individuals with rec(X) chromosomes, including deletions in the pseudoautosomal region 1 (PAR1) at Xp22.33/Yp11.3 and duplications of the distal Xq region including MECP2, revealed a high prevalence of undescended testes (7/8) and micropenis (3/8) in this cohort. Given that micropenis is rare in the general population, but present in 38% of individuals in this cohort, a dosage anomaly at one or both loci may be a significant risk factor for this condition. Therefore, we recommend microarray testing for patients with unexplained micropenis, particularly when accompanied by other phenotypic anomalies.
authors.affiliation: Human Genetics Laboratories, University of Nebraska Medical Center and Munroe-Meyer Institute for Genetics and Rehabilitation, Omaha, Nebraska 68198-5440, USA. jsanmann@unmc.edu
authors.forename: Jennifer N
authors.initials: JN
authors.lastname: Sanmann
authors.forename: Danielle L
authors.initials: DL
authors.lastname: Bishay
authors.forename: Lois J
authors.initials: LJ
authors.lastname: Starr
authors.forename: Carla A
authors.initials: CA
authors.lastname: Bell
authors.forename: Diane L
authors.initials: DL
authors.lastname: Pickering
authors.forename: Jadd M
authors.initials: JM
authors.lastname: Stevens
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Kahler
authors.forename: Ann Haskins
authors.initials: AH
authors.lastname: Olney
authors.forename: G Bradley
authors.initials: GB
authors.lastname: Schaefer
authors.forename: Warren G
authors.initials: WG
authors.lastname: Sanger
mesh_terms: D000015:Abnormalities, Multiple / Q000175:diagnosis / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D041321:Chromosomes, Human, X; D002658:Developmental Disabilities / Q000175:diagnosis / Q000235:genetics; D020440:Gene Duplication; D006801:Humans; D008607:Intellectual Disability / Q000175:diagnosis / Q000235:genetics; D008297:Male; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics*; D014178:Translocation, Genetic
chemical_list: D051783:Methyl-CpG-Binding Protein 2