Unusual X-chromosome inactivation pattern in patients with Xp11.23-p11.22 duplication: Report and review.
In females carrying structural rearrangements of an X-chromosome, cells with the best dosage balance are preferentially selected, frequently resulting in a skewed inactivation pattern and amelioration of the phenotype. The Xp11.23-p11.22 region is involved in a recently described microduplication syndrome associated with severe clinical consequences in males and females, causing intellectual disability, behavior problems, epilepsy with electroencephalogram anomalies, minor facial anomalies, and early onset of puberty. Female carriers usually present an unusual X-chromosome inactivation pattern in favor of the aberrant chromosome, resulting in functional disomy of the duplicated segment. Here, we describe a girl carrying a de novo ∼9.7 Mb Xp11.3-p11.22 duplication of paternal origin and skewed X-chromosome inactivation pattern of the normal X-chromosome. We reviewed other cases previously reported and determined the minimal critical region possibly responsible for this unusual inactivation pattern. The critical region encompasses 36 RefSeq genes, including at least 10 oncogenes and/or genes related to the cell cycle control. We discuss the molecular mechanisms that underlie the positive selection of the cells with the active duplicated chromosome. © 2016 Wiley Periodicals, Inc.
Division of Genetics, Department of Morphology and Genetics, Universidade Federal de São Paulo, São Paulo, Brazil.
Adriana
A
Di-Battista
Division of Genetics, Department of Morphology and Genetics, Universidade Federal de São Paulo, São Paulo, Brazil.
Vera Ayres
VA
Meloni
Department of Biochemistry, Universidade Federal de São Paulo, São Paulo, Brazil.
Magnus Dias
MD
da Silva
Division of Genetics, Department of Morphology and Genetics, Universidade Federal de São Paulo, São Paulo, Brazil.
Mariana
M
Moysés-Oliveira
Division of Genetics, Department of Morphology and Genetics, Universidade Federal de São Paulo, São Paulo, Brazil.
Maria Isabel
MI
Melaragno
D058674:Chromosome Duplication; D041321:Chromosomes, Human, X; D004569:Electroencephalography; D019066:Facies; D005260:Female; D056726:Genetic Association Studies; D006579:Heterozygote; D006801:Humans; D007231:Infant, Newborn; D010641:Phenotype; D010808:Physical Examination; D049951:X Chromosome Inactivation
X-chromosome inactivation; Xp11.23-p11.22 duplication; epilepsy; intellectual disability