How to Cite this Article: Brasil AS, Malaquias AC, Kim CA, Krieger JE, Jorge AAL, Pereira AC, Bertola DR. 2012. KRAS gene mutations in Noonan syndrome familial cases cluster in the vicinity of the switch II region of the G-domain: Report of another family with metopic craniosynostosis. Am J Med Genet Part A. 158A:1178–1184.
KRAS gene mutations in Noonan syndrome familial cases cluster in the vicinity of the switch II region of the G-domain: Report of another family with metopic craniosynostosis†
Article first published online: 9 APR 2012
Copyright © 2012 Wiley Periodicals, Inc.
American Journal of Medical Genetics Part A
Volume 158A, Issue 5, pages 1178–1184, May 2012
How to Cite
Brasil, A. S., Malaquias, A. C., Kim, C. A., Krieger, J. E., Jorge, A. A.L., Pereira, A. C. and Bertola, D. R. (2012), KRAS gene mutations in Noonan syndrome familial cases cluster in the vicinity of the switch II region of the G-domain: Report of another family with metopic craniosynostosis. Am. J. Med. Genet., 158A: 1178–1184. doi: 10.1002/ajmg.a.35270
- Issue published online: 18 APR 2012
- Article first published online: 9 APR 2012
- Manuscript Accepted: 12 JAN 2012
- Manuscript Received: 12 AUG 2011
- Fundação de Amparo a Pesquisa do Estado de São Paulo (FAPESP). Grant Number: 08/50184-2
- Noonan syndrome;
- KRAS gene mutation;
- ectodermal findings;
Noonan syndrome (NS) and Noonan-related disorders [cardio-facio-cutaneous (CFC), Costello, Noonan syndrome with multiple lentigines (NS-ML), and neurofibromatosis-Noonan syndromes (NFNS)] are a group of developmental disorders caused by mutations in genes of the RAS/MAPK pathway. Mutations in the KRAS gene account for only a small proportion of affected Noonan and CFC syndrome patients that present an intermediate phenotype between these two syndromes, with more frequent and severe intellectual disability in NS and less ectodermal involvement in CFC syndrome, as well as atypical clinical findings such as craniosynostosis. Recently, the first familial case with a novel KRAS mutation was described. We report on a second vertical transmission (a mother and two siblings) with a novel mutation (p.M72L), in which the proband has trigonocephaly and the affected mother and sister, prominent ectodermal involvement. Metopic suture involvement has not been described before, expanding the main different cranial sutures which can be affected in NS and KRAS gene mutations. The gene alteration found in the studied family is in close proximity to the one reported in the other familial case (close to the switch II region of the G-domain), suggesting that this specific region of the gene could have less severe effects on intellectual ability than the other KRAS gene mutations found in NS patients and be less likely to hamper reproductive fitness. © 2012 Wiley Periodicals, Inc.