Unraveling unusual X-chromosome patterns during fragile-X syndrome genetic testing.
Clin Chim Acta
; 476: 167-172, 2018 Jan.
Article
en En
| MEDLINE
| ID: mdl-29170104
BACKGROUND: Fragile X syndrome (FXS) is the most common form of inherited intellectual disability (ID). Together with fragile X-associated tremor and ataxia (FXTAS) and fragile X-associated premature ovarian failure (POF)/primary ovarian insufficiency (POI), FXS depends on dysfunctional expression of the FMR1 gene on Xq27.3. In most cases, FXS is caused by a >200 CGG repeats in FMR1 5'-untranslated region (UTR) and by promoter hypermethylation that results in gene silencing. Males and females with unmethylated premutated alleles (repeats between 55 and 200) are at risk for FXTAS and POF/POI. METHODS: FXS molecular testing relied on PCR and methylation-specific Southern blot analysis of the FMR1 5'UTR. Atypical Southern blot patterns were studied by X-chromosome microsatellite analysis, copy number dosage at DMD locus, amelogenin gender-marker analysis and array-comparative genomic hybridization (array-CGH). RESULTS: Six men affected by ID and three women affected by ID and POF/POI underwent FXS molecular testing. They had normal FMR1 CGG repeats, but atypical X chromosome patterns. Further investigations revealed that the six males had Klinefelter syndrome (XXY), one female was a Turner mosaic (X0/XX) and two women had novel rearrangements involving X chromosome. CONCLUSIONS: Diagnostic investigation of atypical patterns at FMR1 locus can address patients and/or their relatives to further verify the condition by performing karyotyping and/or array-CGH.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Ataxia
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Temblor
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Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil
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Genes Ligados a X
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Síndrome del Cromosoma X Frágil
Tipo de estudio:
Diagnostic_studies
Límite:
Adolescent
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Adult
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Child
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Female
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Humans
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Male
Idioma:
En
Revista:
Clin Chim Acta
Año:
2018
Tipo del documento:
Article
País de afiliación:
Italia
Pais de publicación:
Países Bajos