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SOS1 is the second most common Noonan gene but plays no major role in cardio-facio-cutaneous syndrome.

ABSTRACT: BACKGROUND: Heterozygous gain-of-function mutations in various genes encoding proteins of the Ras-MAPK signalling cascade have been identified as the genetic basis of Noonan syndrome (NS) and cardio-facio-cutaneous syndrome (CFCS). Mutations of SOS1, the gene encoding a guanine nucleotide exchange factor for Ras, have been the most recent discoveries in patients with NS, but this gene has not been studied in patients with CFCS. METHODS AND RESULTS: We investigated SOS1 in a large cohort of patients with disorders of the NS-CFCS spectrum, who had previously tested negative for mutations in PTPN11, KRAS, BRAF, MEK1 and MEK2. Missense mutations of SOS1 were discovered in 28% of patients with NS. In contrast, none of the patients classified as having CFCS was found to carry a pathogenic sequence change in this gene. CONCLUSION: We have confirmed SOS1 as the second major gene for NS. Patients carrying mutations in this gene have a distinctive phenotype with frequent ectodermal anomalies such as keratosis pilaris and curly hair. However, the clinical picture associated with SOS1 mutations is different from that of CFCS. These findings corroborate that, despite being caused by gain-of-function mutations in molecules belonging to the same pathway, NS and CFCS scarcely overlap genotypically.

SUBMITTER: Zenker M

PROVIDER: S-EPMC2597961 | biostudies-literature | 2007 Oct

REPOSITORIES: biostudies-literature

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SOS1 is the second most common Noonan gene but plays no major role in cardio-facio-cutaneous syndrome.

Zenker Martin M Horn Denise D Wieczorek Dagmar D Allanson Judith J Pauli Silke S van der Burgt Ineke I Doerr Helmuth-Guenther HG Gaspar Harald H Hofbeck Michael M Gillessen-Kaesbach Gabriele G Koch Andreas A Meinecke Peter P Mundlos Stefan S Nowka Anja A Rauch Anita A Reif Silke S von Schnakenburg Christian C Seidel Heide H Wehner Lars-Erik LE Zweier Christiane C Bauhuber Susanne S Matejas Verena V Kratz Christian P CP Thomas Christoph C Kutsche Kerstin K

Journal of medical genetics 20070623 10

<h4>Background</h4>Heterozygous gain-of-function mutations in various genes encoding proteins of the Ras-MAPK signalling cascade have been identified as the genetic basis of Noonan syndrome (NS) and cardio-facio-cutaneous syndrome (CFCS). Mutations of SOS1, the gene encoding a guanine nucleotide exchange factor for Ras, have been the most recent discoveries in patients with NS, but this gene has not been studied in patients with CFCS.<h4>Methods and results</h4>We investigated SOS1 in a large co ...[more]

PMID: 17586837

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Project description:Backgroundcardio-facio-cutaneous syndrome is a rare genetic disorder affecting less than 900 people in the world. It is mainly characterized by craniofacial, dermatologic and cardiac defects, but also gastroenterological symptoms may be present, ranging from feeding difficulties to gastroesophageal reflux and constipation.In this report we describe a case of this syndrome characterized by severe feeding and growth difficulties, with a particular focus on the management of gastroenterological complications.Case presentationthe patient was a caucasian male affected by Cardio-Facio-Cutaneous syndrome who presented feeding difficulties already a few hours after birth. These symptoms worsened in the following months and lead to a complete growth arrest and malnutrition. He was first treated with a nasogastric tube placement. Subsequently, a laparoscopic Nissen fundoplication and a laparoscopic Stamm gastrostomy were performed. The child was fed with nocturnal enteral nutrition and diurnal oral and enteral nutrition. Eventually the patient resumed feeding validly and regained adequate growth.Conclusionthis paper aims to bring to light a complex rare syndrome that infrequently comes to the attention of the pediatricians and whose diagnosis is not always straightforward. We also highlight the possible complications under a gastroenterologic point of view. Our contribution can be helpful to the pediatrician in the first diagnostic suspect of this syndrome. In particular, it is worth highlighting that -in an infant with Noonan-like features- symptoms like suction or swallowing problems, vomiting and feeding difficulties should orient towards the diagnosis of a Cardio-facio-cutaneous syndrome. It is also important to stress that its related gastroenterological issues may lead to severe growth failure and therefore the role of the gastroenterologist is key to manage supplemental feeding and to establish whether a nasogastric or gastrostomic tube placement is necessary.

Dataset Information

SOS1 is the second most common Noonan gene but plays no major role in cardio-facio-cutaneous syndrome.

Publications

SOS1 is the second most common Noonan gene but plays no major role in cardio-facio-cutaneous syndrome.

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