Recent advances in RASopathies

Abstract

RASopathies or RAS/mitogen-activated protein kinase (MAPK) syndromes are a group of phenotypically overlapping syndromes caused by germline mutations that encode components of the RAS/MAPK signaling pathway. These disorders include neurofibromatosis type I, Legius syndrome, Noonan syndrome, Noonan syndrome with multiple lentigines (formerly called LEOPARD syndrome), Costello syndrome, cardiofaciocutaneous (CFC) syndrome, Noonan-like syndrome, hereditary gingival fibromatosis and capillary malformation-arteriovenous malformation. Recently, novel gene variants, including RIT1, RRAS, RASA2, A2ML1, SOS2 and LZTR1, have been shown to be associated with RASopathies, further expanding the disease entity. Although further analysis will be needed, these findings will help to better elucidate an understanding of the pathogenesis of these disorders and will aid in the development of potential therapeutic approaches. In this review, we summarize the novel genes that have been reported to be associated with RASopathies and highlight the cardiovascular abnormalities that may arise in affected individuals.

Targeted sequencing of refractory myeloma reveals a high incidence of mutations in CRBN and Ras pathway genes

“…Mutations in this gene have been described in various malignancies, including colorectal, skin, lung, and endometrial cancers; however, the biological function of the gene has not yet been fully deciphered, and it is hypothesized to be a RAS inhibitor. 56 Of note, 1 of the patients (#1) with a Val600Glu BRAF mutation harbored an additional nonsense mutation in RASA2, which may contribute to further MAPK activation in this patient.…”

NOONAN SYNDROME AS RESULT OF MUTATION p. S257L OF GENE RAF1: CLINICAL CASE AND REVIEW

“…При возникновении мутации de novo риск рождения ребёнка с таким же заболеванием в этой супружеской паре минимален. , Zaklyazminskaya Е. V. 1,3 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.…”

“…За последние годы знания о генетических основах синдрома Нунан существенно расширились: так, в базе данных OMIM к настоящему моменту имеются сведения о минимум 10 генетических формах синдрома. Тем не менее, у 20-30% пациентов не обнаруживается мутаций в известных на текущий момент генах [3].…”

Further Evidence for the Implication of LZTR1, a Gene not Associated with the Ras-Mapk Pathway, in the Pathogenesis of Noonan Syndrome

“…Recently, novel gene variants affecting RRAS, RASA2, A2ML1, SOS2 and LZTR1 have been shown to be associated with NS and RASopathies [12].…”