Duplication Xp11.22-p14 in females: does X-inactivation help in assessing their significance?
Am J Med Genet A
; 167A(3): 553-62, 2015 Mar.
Article
em En
| MEDLINE
| ID: mdl-25691408
ABSTRACT
In females, large duplications in Xp often lead to preferential inactivation of the aberrant X chromosome and a normal phenotype. Recently, a recurrent â¼4.5 Mb microduplication of Xp11.22-p11.23 was found in females with developmental delay/intellectual disability and other neurodevelopmental disorders (speech development disorder, epilepsy or EEG anomalies, autism spectrum disorder, or behavioral disorder). Unexpectedly, most of them showed preferential inactivation of the normal X chromosome. We describe five female patients carrying de novo Xp duplications encompassing p11.23. Patient 1 carried the recurrent microduplication Xp11.22-p11.23, her phenotype and X-chromosome inactivation (XI) pattern was consistent with previous reports. The other four patients had novel Xp duplications. Two were monozygotic twins with a similar phenotype to Patient 1 and unfavorable XI skewing carrying an overlapping â¼5 Mb duplication of Xp11.23-p11.3. Patient 4 showed a duplication of â¼5.5 Mb comparable to the twins but had a more severe phenotype and unskewed XI. Patient 5 had a â¼8.5 Mb duplication Xp11.23-p11.4 and presented with mild ID, epilepsy, behavioral problems, and inconsistent results of XI analysis. A comparison of phenotype, size and location of the duplications and XI patterns in Patients 1-5 and previously reported females with overlapping duplications provides further evidence that microduplications encompassing Xp11.23 are associated with ID and other neurodevelopmental disorders in females. To further assess the implication of XI for female carriers, we recommend systematic analysis of XI pattern in any female with X imbalances that are known or suspected to be pathogenic.
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Base de dados:
MEDLINE
Assunto principal:
Transtornos dos Cromossomos Sexuais
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Cromossomos Humanos X
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Inativação do Cromossomo X
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Duplicação Cromossômica
Tipo de estudo:
Diagnostic_studies
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Prognostic_studies
Limite:
Adolescent
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Adult
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Child
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Child, preschool
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Female
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Humans
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article