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MECP2 duplication: Possible cause of severe phenotype in females
Author(s) -
Scott Schwoerer Jessica,
Laffin Jennifer,
Haun Joanne,
Raca Gordana,
Friez Michael J.,
Giampietro Philip F.
Publication year - 2014
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.36380
Subject(s) - gene duplication , mecp2 , proband , genetics , hypotonia , intellectual disability , phenotype , comparative genomic hybridization , biology , gene , psychology , chromosome , mutation
MECP2 duplication syndrome, originally described in 2005, is an X‐linked neurodevelopmental disorder comprising infantile hypotonia, severe to profound intellectual disability, autism or autistic‐like features, spasticity, along with a variety of additional features that are not always clinically apparent. The syndrome is due to a duplication (or triplication) of the gene methyl CpG binding protein 2 ( MECP2 ). To date, the disorder has been described almost exclusively in males. Female carriers of the duplication are thought to have no or mild phenotypic features. Recently, a phenotype for females began emerging. We describe a family with ∼290 kb duplication of Xq28 region that includes the MECP2 gene where the proposita and affected family members are female. Twin sisters, presumed identical, presented early with developmental delay, and seizures. Evaluation of the proposita at 25 years of age included microarray comparative genomic hybridization (aCGH) which revealed the MECP2 gene duplication. The same duplication was found in the proposita's sister, who is more severely affected, and the proband's mother who has mild intellectual disability and depression. X‐chromosome inactivation studies showed significant skewing in the mother, but was uninformative in the twin sisters. We propose that the MECP2 duplication caused for the phenotype of the proband and her sister. These findings support evidence for varied severity in some females with MECP2 duplications. © 2014 Wiley Periodicals, Inc.