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1p13.2 deletion displays clinical features overlapping Noonan syndrome, likely related to NRAS gene haploinsufficiency
Univ Fed Minas Gerais, Fac Med, Lab Genom Clin, Belo Horizonte, MG, Brazil..
Univ Fed Minas Gerais, Inst Ciencias Biol, Dept Bioquim & Imunol, Belo Horizonte, MG, Brazil..
Univ Fed Minas Gerais, Fac Med, Lab Genom Clin, Belo Horizonte, MG, Brazil..
Lab Gene Nucl Genet Med, Belo Horizonte, MG, Brazil..
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2016 (English)In: Genetics and Molecular Biology, ISSN 1415-4757, E-ISSN 1678-4685, Vol. 39, no 3, 349-357 p.Article in journal (Refereed) Published
Abstract [en]

Deletion-induced hemizygosity may unmask deleterious autosomal recessive variants and be a cause of the phenotypic variability observed in microdeletion syndromes. We performed complete exome sequencing (WES) analysis to examine this possibility in a patient with 1p13.2 microdeletion. Since the patient displayed clinical features suggestive of Noonan Syndrome (NS), we also used WES to rule out the presence of pathogenic variants in any of the genes associated with the different types of NS. We concluded that the clinical findings could be attributed solely to the 1p13.2 haploinsufficiency. Retrospective analysis of other nine reported patients with 1p13.2 microdeletions showed that six of them also presented some characteristics of NS. In all these cases, the deleted segment included the NRAS gene. Gain-of-function mutations of NRAS gene are causally related to NS type 6. Thus, it is conceivable that NRAS haploinsufficiency and gain-of-function mutations may have similar clinical consequences. The same phenomenon has been described for two other genes belonging to the Ras/MAPK pathway: MAP2K2 and SHOC2. In conclusion, we here report genotype-phenotype correlations in patients with chromosome 1p13.2 microdeletions and we propose that NRAS may be a critical gene for the NS characteristics in the patients.

Place, publisher, year, edition, pages
2016. Vol. 39, no 3, 349-357 p.
Keyword [en]
1p13.2 deletion, Noonan syndrome type 6, NRAS gene, RASopathy, unmasking heterozygosity
National Category
Basic Medicine
URN: urn:nbn:se:uu:diva-304521DOI: 10.1590/1678-4685-GMB-2016-0049ISI: 000382151700006PubMedID: 27561113OAI: diva2:1034472
Available from: 2016-10-12 Created: 2016-10-06 Last updated: 2016-10-12Bibliographically approved

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Thuresson, Ann-CharlotteAnnerén, Göran
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