Phenotypic variability associated with the invariant SHOC2 c.4A>G (p.Ser2Gly) missense mutation.

Authors:
Giuseppina Baldassarre
Giuseppina Baldassarre
University of Torino
Torino | Italy
Alessandro Mussa
Alessandro Mussa
University of Torino
Italy
Elena Banaudi
Elena Banaudi
University of Torino
Italy
Cesare Rossi
Cesare Rossi
Policlinico S.Orsola-Malpighi
Bologna | Italy
Marco Tartaglia
Marco Tartaglia
Genetics and Rare Diseases Research Division
United States
Margherita Silengo
Margherita Silengo
University of Torino
Torino | Italy
Giovanni Battista Ferrero
Giovanni Battista Ferrero
University of Torino
Italy

Am J Med Genet A 2014 Dec 20;164A(12):3120-5. Epub 2014 Oct 20.

Department of Paediatrics, University of Torino, Torino, Italy.

Noonan-like syndrome with loose anagen hair (NS/LAH; OMIM 607721) is a developmental disorder clinically related to Noonan syndrome (NS) and characterized by facial dysmorphisms, postnatal growth retardation, cardiac anomalies (in particular dysplasia of the mitral valve and septal defects), variable neurocognitive impairment, and florid ectodermal features. A distinctive trait of NS/LAH is its association with easily pluckable, slow growing, sparse, and thin hair. This rare condition is due to the invariant c.4A > G missense (p.Ser2Gly) change in SHOC2, which encodes a regulatory protein that participate in RAS signaling. Here we report two patients with molecularly confirmed NS/LAH, with extremely different phenotypic expression, in particular concerning the severity of the cardiac phenotype and neurocognitive profile. While the first available clinical records outlined a relatively homogeneous phenotype in NS/LAH, the present data emphasize that the phenotype spectrum associated with this invariant mutation is wider than previously recognized.

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http://dx.doi.org/10.1002/ajmg.a.36697DOI Listing
December 2014
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