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- Title
Classical fragile-X phenotype in a female infant disclosed by comprehensive genomic studies.
- Authors
Jorge, Paula; Garcia, Elsa; Gonçalves, Ana; Marques, Isabel; Maia, Nuno; Rodrigues, Bárbara; Santos, Helena; Fonseca, Jacinta; Soares, Gabriela; Correia, Cecília; Reis-Lima, Margarida; Cirigliano, Vincenzo; Santos, Rosário
- Abstract
Background: We describe a female infant with Fragile-X syndrome, with a fully expanded <italic>FMR1</italic> allele and preferential inactivation of the homologous X-chromosome carrying a de novo deletion. This unusual and rare case demonstrates the importance of a detailed genomic approach, the absence of which could be misguiding, and calls for reflection on the current clinical and diagnostic workup for developmental disabilities. Case presentation: We present a female infant, referred for genetic testing due to psychomotor developmental delay without specific dysmorphic features or relevant family history. <italic>FMR1</italic> mutation screening revealed a methylated full mutation and a normal but inactive <italic>FMR1</italic> allele, which led to further investigation. Complete skewing of X-chromosome inactivation towards the paternally-inherited normal-sized <italic>FMR1</italic> allele was found. No pathogenic variants were identified in the <italic>XIST</italic> promoter. Microarray analysis revealed a 439 kb deletion at Xq28, in a region known to be associated with extreme skewing of X-chromosome inactivation. Conclusions: Overall results enable us to conclude that the developmental delay is the cumulative result of a methylated <italic>FMR1</italic> full mutation on the active X-chromosome and the inactivation of the other homologue carrying the de novo 439 kb deletion. Our findings should be taken into consideration in future guidelines for the diagnostic workup on the diagnosis of intellectual disabilities, particularly in female infant cases.
- Subjects
DIAGNOSIS of fragile X syndrome; INFANT diseases; DELETION mutation; X chromosome; GENOMICS; GENE silencing; GENETICS
- Publication
BMC Medical Genetics, 2018, Vol 19, Issue 1, pN.PAG
- ISSN
1471-2350
- Publication type
Case Study
- DOI
10.1186/s12881-018-0589-6