NOONAN SYNDROME AS RESULT OF MUTATION p. S257L OF GENE RAF1: CLINICAL CASE AND REVIEW
https://doi.org/10.15829/1560-4071-2016-10-93-97
Abstract
Noonan syndrome is clinically and genetically heterogenic disease caused by mutations in genes coding the proteins of universal cascade of cellular signalling Ras-MAPK. Recently, about 10 genes known, with mutations leading to the disease development. Among multiple manifestations of the syndrome most clinically and prognostically significant are disorders of cardiovascular system, including hypertrophic cardiomyopathy and pulmonary artery stenosis. In the article, a case is presented of sporadic Noonan syndrome in 5-year old child with left ventricle hypertrophy and obstruction of outgoing flow. Genetic investigation revealed mutation p. S257L of gene RAF1, occurred de novo. Appearance of mutation de novo does not lead to increased risk of the second child birth with same disease by the parents.
About the Authors
A. A. Bukaeva
V. B. Petrovskiy Russian National Research Centre of Surgery, Moscow
Russian Federation
Russian Federation
N. P. Kotlukova
Z. A. B ashlyaeva Pediatric City Clinical Hospital. Bashlyaeva, Moscow
N. I. Pirogov Russian National Research Medical University (RNRMU), Moscow, Russia
Russian Federation
Russian Federation
E. V. Zaklyazminskaya
V. B. Petrovskiy Russian National Research Centre of Surgery, Moscow
Z. A. B ashlyaeva Pediatric City Clinical Hospital. Bashlyaeva, Moscow
Russian Federation
Russian Federation
References
1. Jung Min Ko. Genetic Syndromes associated with Congenital Heart Disease. Korean Circ J. 2015 Sep; 45(5): 357–61.
2. Roberts AE, Allanson JE, Tartaglia M, et al. Noonan syndrome (review). Lancet. 2013 Jan 26;381(9863):333-42.
3. Aoki Y., Niihori T ., Inoue S., Matsubara Y. Recent advances in RASopathies. Journal of Human Genetics 2016; 61: 33-9.
4. Alicia A. Romano, Judith E. Allanson, Jovanna Dahlgren, et al. Noonan Syndrome: Clinical Features, Diagnosis, and Management Guidelines. Pediatrics 2010; 126; 746.
5. Zenker M, Lehmann K, Schulz AL, et al. Expansion of the genotypic and phenotypic spectrum in patients with KRAS germline mutations. J Med Genet 2007; 44: 131-35.
6. Pandit B, Sarkozy A, Pennacchio LA, et al. Gain-of-function RAF1 mutations cause Noonan and LEOPARD syndromes with hypertrophic cardiomyopathy. Nat Genet. 2007; Aug; 39(8): 1007-12.
7. Kobayashi T, Aoki Y, Niihori T, et al. Molecular and Clinical Analysis of RAF1 in Noonan Syndrome and Related Disorders: Dephosphorylation of Serine 259 as the Essential Mechanism for Mutant Activation. Hum Mutat 2010; 31: 284-94.
8. Hopper RK, Feinstein JA, Manning MA, et al. 2015. Neonatal pulmonary arterial hypertension and Noonan syndrome: Two fatal cases with a specific RAF1 mutation. Am J Med Genet Part A 167A: 882-5.
9. Kuburović V, Vukomanović V, Carcavilla A, et al. Two cases of LEOPARD syndrome — RAF1 mutations firstly described in children. Turk J Pediatr 2011; 53: 687-91.
Review
For citations:
Bukaeva A.A., Kotlukova N.P., Zaklyazminskaya E.V. NOONAN SYNDROME AS RESULT OF MUTATION p. S257L OF GENE RAF1: CLINICAL CASE AND REVIEW. Russian Journal of Cardiology. 2016;(10):93-97. (In Russ.) https://doi.org/10.15829/1560-4071-2016-10-93-97
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