A splicing mutation of the HMGA2 gene is associated with Silver-Russell syndrome phenotype.
J Hum Genet
; 60(6): 287-93, 2015 Jun.
Article
em En
| MEDLINE
| ID: mdl-25809938
Silver-Russell syndrome (SRS) is a heterogeneous disorder characterized by intrauterine and post-natal growth retardation, dysmorphic facial features and body asymmetry. About 50% of the patients carry (epi)genetic alterations involving chromosomes 7 or 11.The high proportion of patients with unidentified molecular etiology suggests the involvement of other genes. Interestingly, SRS patients share clinical features with the 12q14 microdeletion syndrome, characterized by several deletions with a 2.6 Mb region of overlap. Among the genes present in this interval, high mobility AT-hook 2 (HMGA2) appears to be the most likely cause of the growth deficiency, due to its described growth control function. To define the role of HMGA2 in SRS, we looked for 12q14 chromosome imbalances and HMGA2 mutations in a cohort of 45 patients with growth retardation and SRS-like phenotype but no 11p15 (epi)mutations or maternal uniparental disomy of chromosome 7 (matUPD7). We identified a novel 7 bp intronic deletion in HMGA2 present in heterozygosity in the proband and her mother both displaying the typical features of SRS. We demonstrated that the deletion affected normal splicing, indicating that it is a likely cause of HMGA2 deficiency. This study provides the first evidence that a loss-of-function mutation of HMGA2 can be associated with a familial form of SRS. We suggest that HMGA2 mutations leading to haploinsufficiency should be investigated in the SRS patients negative for the typical 11p15 (epi)mutations and matUPD7.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteína HMGA2
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Síndrome de Silver-Russell
Tipo de estudo:
Observational_studies
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Risk_factors_studies
Limite:
Child, preschool
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Female
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Humans
Idioma:
En
Revista:
J Hum Genet
Assunto da revista:
GENETICA MEDICA
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
Itália