Molecular and clinical insights into complex genomic rearrangements related to MECP2 duplication syndrome.
Eur J Med Genet
; 64(12): 104367, 2021 Dec.
Article
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| MEDLINE
| ID: mdl-34678473
ABSTRACT
MECP2 duplication syndrome (MDS) is caused by copy number variation (CNV) spanning the MECP2 gene at Xq28 and is a major cause of intellectual disability (ID) in males. Herein, we describe two unrelated males harboring non-recurrent complex Xq28 rearrangements associated with MDS. Copy number gains were initially detected by quantitative real-time polymerase chain reaction and further delineated by high-resolution array comparative genomic hybridization, familial segregation, expression analysis and X-chromosome inactivation (XCI) evaluation in a carrier mother. SNVs within the rearrangements and/or fluorescent in situ hybridization (FISH) were used to assess the parental origin of the rearrangements. Patient 1 exhibited an intrachromosomal rearrangement, whose structure is consistent with a triplicated segment presumably embedded in an inverted orientation between two duplicated sequences (DUP-TRP/INV-DUP). The rearrangement was inherited from the carrier mother, who exhibits extreme XCI skewing and subtle psychiatric symptoms. Patient 2 presented a de novo (X;Y) unbalanced translocation resulting in duplication of Xq28 and deletion of Yp, originated in the paternal gametogenesis. Neurodevelopmental trajectory and non-neurological symptoms were consistent with previous reports, with the exception of cerebellar vermis hypoplasia in patient 2. Although both patients share the core MDS phenotype, patient 1 showed MECP2 transcript levels in blood similar to controls. Understanding the molecular mechanisms related to MDS is essential for designing targeted therapeutic strategies.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Reordenamiento Génico
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Duplicación de Gen
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Proteína 2 de Unión a Metil-CpG
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Duplicación Cromosómica
Límite:
Adolescent
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Adult
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Child
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Child, preschool
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Humans
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Infant
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Male
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Middle aged
Idioma:
En
Revista:
Eur J Med Genet
Asunto de la revista:
GENETICA MEDICA
Año:
2021
Tipo del documento:
Article
País de afiliación:
Brasil