title: Phenotypic variability associated with the invariant SHOC2 c.4A>G (p.Ser2Gly) missense mutation.
abstract: 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.
authors.affiliation: Department of Paediatrics, University of Torino, Torino, Italy.
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Baldassarre
authors.forename: Alessandro
authors.initials: A
authors.lastname: Mussa
authors.forename: Elena
authors.initials: E
authors.lastname: Banaudi
authors.forename: Cesare
authors.initials: C
authors.lastname: Rossi
authors.forename: Marco
authors.initials: M
authors.lastname: Tartaglia
authors.forename: Margherita
authors.initials: M
authors.lastname: Silengo
authors.forename: Giovanni Battista
authors.initials: GB
authors.lastname: Ferrero
mesh_terms: D004569:Electroencephalography; D006330:Heart Defects, Congenital / Q000235:genetics / Q000473:pathology*; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics / Q000473:pathology*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D007558:Italy; D058247:Loose Anagen Hair Syndrome / Q000235:genetics* / Q000473:pathology*; D008279:Magnetic Resonance Imaging; D008297:Male; D020125:Mutation, Missense / Q000235:genetics*; D009634:Noonan Syndrome / Q000235:genetics* / Q000473:pathology*; D010641:Phenotype
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C112913:SHOC2 protein, human
keywords: RAS/MAPK; SHOC2; noonan syndrome; rasopathies