症候性頭蓋縫合早期癒合症 [DS:H00458]
ヌーナン症候群類縁疾患 [DS:H00523]

Tartaglia M, Gelb BD, Zenker M

Noonan syndrome and clinically related disorders.

Best Pract Res Clin Endocrinol Metab 25:161-79 (2011)
DOI:10.1016/j.beem.2010.09.002

Tartaglia M, Mehler EL, Goldberg R, Zampino G, Brunner HG, Kremer H, van der Burgt I, Crosby AH, Ion A, Jeffery S, Kalidas K, Patton MA, Kucherlapati RS, Gelb BD

Mutations in PTPN11, encoding the protein tyrosine phosphatase SHP-2, cause Noonan syndrome.

Nat Genet 29:465-8 (2001)
DOI:10.1038/ng772

Schubbert S, Zenker M, Rowe SL, Boll S, Klein C, Bollag G, van der Burgt I, Musante L, Kalscheuer V, Wehner LE, Nguyen H, West B, Zhang KY, Sistermans E, Rauch A, Niemeyer CM, Shannon K, Kratz CP

Germline KRAS mutations cause Noonan syndrome.

Nat Genet 38:331-6 (2006)
DOI:10.1038/ng1748

Roberts AE, Araki T, Swanson KD, Montgomery KT, Schiripo TA, Joshi VA, Li L, Yassin Y, Tamburino AM, Neel BG, Kucherlapati RS

Germline gain-of-function mutations in SOS1 cause Noonan syndrome.

Nat Genet 39:70-4 (2007)
DOI:10.1038/ng1926

Pandit B, Sarkozy A, Pennacchio LA, Carta C, Oishi K, Martinelli S, Pogna EA, Schackwitz W, Ustaszewska A, Landstrom A, Bos JM, Ommen SR, Esposito G, Lepri F, Faul C, Mundel P, Lopez Siguero JP, Tenconi R, Selicorni A, Rossi C, Mazzanti L, Torrente I, Marino B, Digilio MC, Zampino G, Ackerman MJ, Dallapiccola B, Tartaglia M, Gelb BD

Gain-of-function RAF1 mutations cause Noonan and LEOPARD syndromes with hypertrophic cardiomyopathy.

Nat Genet 39:1007-12 (2007)
DOI:10.1038/ng2073

Cirstea IC, Kutsche K, Dvorsky R, Gremer L, Carta C, Horn D, Roberts AE, Lepri F, Merbitz-Zahradnik T, Konig R, Kratz CP, Pantaleoni F, Dentici ML, Joshi VA, Kucherlapati RS, Mazzanti L, Mundlos S, Patton MA, Silengo MC, Rossi C, Zampino G, Digilio C, Stuppia L, Seemanova E, Pennacchio LA, Gelb BD, Dallapiccola B, Wittinghofer A, Ahmadian MR, Tartaglia M, Zenker M

A restricted spectrum of NRAS mutations causes Noonan syndrome.

Nat Genet 42:27-9 (2010)
DOI:10.1038/ng.497

Sarkozy A, Carta C, Moretti S, Zampino G, Digilio MC, Pantaleoni F, Scioletti AP, Esposito G, Cordeddu V, Lepri F, Petrangeli V, Dentici ML, Mancini GM, Selicorni A, Rossi C, Mazzanti L, Marino B, Ferrero GB, Silengo MC, Memo L, Stanzial F, Faravelli F, Stuppia L, Puxeddu E, Gelb BD, Dallapiccola B, Tartaglia M

Germline BRAF mutations in Noonan, LEOPARD, and cardiofaciocutaneous syndromes: molecular diversity and associated phenotypic spectrum.

Hum Mutat 30:695-702 (2009)
DOI:10.1002/humu.20955

Aoki Y, Niihori T, Banjo T, Okamoto N, Mizuno S, Kurosawa K, Ogata T, Takada F, Yano M, Ando T, Hoshika T, Barnett C, Ohashi H, Kawame H, Hasegawa T, Okutani T, Nagashima T, Hasegawa S, Funayama R, Nagashima T, Nakayama K, Inoue S, Watanabe Y, Ogura T, Matsubara Y

Gain-of-function mutations in RIT1 cause Noonan syndrome, a RAS/MAPK pathway syndrome.

Am J Hum Genet 93:173-80 (2013)
DOI:10.1016/j.ajhg.2013.05.021

Yamamoto GL, Aguena M, Gos M, Hung C, Pilch J, Fahiminiya S, Abramowicz A, Cristian I, Buscarilli M, Naslavsky MS, Malaquias AC, Zatz M, Bodamer O, Majewski J, Jorge AA, Pereira AC, Kim CA, Passos-Bueno MR, Bertola DR

Rare variants in SOS2 and LZTR1 are associated with Noonan syndrome.

J Med Genet 52:413-21 (2015)
DOI:10.1136/jmedgenet-2015-103018

Higgins EM, Bos JM, Mason-Suares H, Tester DJ, Ackerman JP, MacRae CA, Sol-Church K, Gripp KW, Urrutia R, Ackerman MJ

Elucidation of MRAS-mediated Noonan syndrome with cardiac hypertrophy.

JCI Insight 2:e91225 (2017)
DOI:10.1172/jci.insight.91225

Capri Y, Flex E, Krumbach OHF, Carpentieri G, Cecchetti S, Lissewski C, Rezaei Adariani S, Schanze D, Brinkmann J, Piard J, Pantaleoni F, Lepri FR, Goh ES, Chong K, Stieglitz E, Meyer J, Kuechler A, Bramswig NC, Sacharow S, Strullu M, Vial Y, Vignal C, Kensah G, Cuturilo G, Kazemein Jasemi NS, Dvorsky R, Monaghan KG, Vincent LM, Cave H, Verloes A, Ahmadian MR, Tartaglia M, Zenker M

Activating Mutations of RRAS2 Are a Rare Cause of Noonan Syndrome.

Am J Hum Genet 104:1223-1232 (2019)
DOI:10.1016/j.ajhg.2019.04.013

Motta M, Pannone L, Pantaleoni F, Bocchinfuso G, Radio FC, Cecchetti S, Ciolfi A, Di Rocco M, Elting MW, Brilstra EH, Boni S, Mazzanti L, Tamburrino F, Walsh L, Payne K, Fernandez-Jaen A, Ganapathi M, Chung WK, Grange DK, Dave-Wala A, Reshmi SC, Bartholomew DW, Mouhlas D, Carpentieri G, Bruselles A, Pizzi S, Bellacchio E, Piceci-Sparascio F, Lissewski C, Brinkmann J, Waclaw RR, Waisfisz Q, van Gassen K, Wentzensen IM, Morrow MM, Alvarez S, Martinez-Garcia M, De Luca A, Memo L, Zampino G, Rossi C, Seri M, Gelb BD, Zenker M, Dallapiccola B, Stella L, Prada CE, Martinelli S, Flex E, Tartaglia M

Enhanced MAPK1 Function Causes a Neurodevelopmental Disorder within the RASopathy Clinical Spectrum.

Am J Hum Genet 107:499-513 (2020)
DOI:10.1016/j.ajhg.2020.06.018

Motta M, Fasano G, Gredy S, Brinkmann J, Bonnard AA, Simsek-Kiper PO, Gulec EY, Essaddam L, Utine GE, Guarnetti Prandi I, Venditti M, Pantaleoni F, Radio FC, Ciolfi A, Petrini S, Consoli F, Vignal C, Hepbasli D, Ullrich M, de Boer E, Vissers LELM, Gritli S, Rossi C, De Luca A, Ben Becher S, Gelb BD, Dallapiccola B, Lauri A, Chillemi G, Schuh K, Cave H, Zenker M, Tartaglia M

SPRED2 loss-of-function causes a recessive Noonan syndrome-like phenotype.

Am J Hum Genet 108:2112-2129 (2021)
DOI:10.1016/j.ajhg.2021.09.007