Pendred syndrome (PS) is an autosomal recessive disorder due to mutations in the SLC26A4 gene (chr7q22. 3) and characterized by sensorineural hearing loss and variable thyroid phenotype. Silver-Russell syndrome (SRS) is a heterogeneous imprinting disorder including severe intrauterine and postnatal growth retardation, and dysmorphic features. Maternal uniparental disomy of either the whole chromosome 7 (upd(7)mat) or 7q (upd(7q)mat) is one of the multiple mechanisms impacting the expression of imprinted genes in SRS, and is associated with milder clinical features. Here, we report genetic and clinical characterization of a female child with PS, postnatal growth retardation, and minor dysmorphic features. A gross homozygous deletion of SLC26A4 exons 17-20 was suspected by Sanger sequencing and then confirmed by array-CGH. Moreover, an insertion of about 1 kb of the CCDC126 gene (7p15.3), which does not appear to be clinically relevant, was detected. The possible occurrence of a balanced rearrangement between 7p and 7q was excluded. The absence of the deletion in the father led to the investigation of upd, and microsatellite segregation analysis revealed a segmental 7q (upd(7q)mat), leading to SLC26A4 homozygosity and responsible for both PS and SRS-like traits. The proband matched 3 out of 6 major SRS criteria. In conclusion, this is the first report of uniparental isodisomy encompassing almost the whole long arm of chromosome 7 resulting in PS and SRS-like features. Whereas, the inner ear phenotype of PS is typical, the clinical features suggestive of SRS might have been overlooked.
Segmental Maternal UPD of Chromosome 7q in a Patient With Pendred and Silver Russell Syndromes-Like Features / V. Cirello, V. Giorgini, C. Castronovo, S. Marelli, E. Mainini, A. Sironi, M. Recalcati, M. Pessina, D. Giardino, L. Larizza, L. Persani, P. Finelli, S. Russo, L. Fugazzola. - In: FRONTIERS IN GENETICS. - ISSN 1664-8021. - 9(2018 Nov), pp. 600.1-600.9.
|Titolo:||Segmental Maternal UPD of Chromosome 7q in a Patient With Pendred and Silver Russell Syndromes-Like Features|
CIRELLO, VALENTINA (Corresponding)
|Parole Chiave:||SLC26A4; pendred syndrome; post-natal growth retardation; silver-russell syndrome; uniparental disomy|
|Settore Scientifico Disciplinare:||Settore MED/13 - Endocrinologia|
Settore MED/03 - Genetica Medica
|Data di pubblicazione:||nov-2018|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.3389/fgene.2018.00600|
|Appare nelle tipologie:||01 - Articolo su periodico|