Skip to main content
Erschienen in: European Journal of Pediatrics 8/2005

01.08.2005 | Original Paper

A novel mutation in the PTPN11 gene in a patient with Noonan syndrome and rapidly progressive hypertrophic cardiomyopathy

verfasst von: Kunihiko Takahashi, Shigetoyo Kogaki, Shunji Kurotobi, Sayaka Nasuno, Makiko Ohta, Hitomi Okabe, Kazuko Wada, Norio Sakai, Masako Taniike, Keiichi Ozono

Erschienen in: European Journal of Pediatrics | Ausgabe 8/2005

Einloggen, um Zugang zu erhalten

Abstract

A male infant with clinical features of Noonan syndrome and rapidly progressive hypertrophic cardiomyopathy is reported. He manifested severe heart failure and failure to thrive. Administration of propranolol and cibenzoline improved ventricular outflow tract obstruction, leading to catch-up growth. Genetic analysis of the patient revealed a novel missense mutation in the PTPN11 gene. Conclusion:This is the first description of a patient with a Gln510Glu mutation in the protein-tyrosine phosphatase, non-receptor type 11 gene. This specific mutation may be associated with a rapidly progressive hypertrophic cardiomyopathy.
Literatur
1.
Zurück zum Zitat Bertola DR, Kim CA, Sugayama SM, Albano LM, Wagenfuhr J, Moyses RL, Gonzalez CH (2000) Cardiac findings in 31 patients with Noonan’s syndrome. Arq Bras Cardiol 75: 409–412CrossRefPubMed Bertola DR, Kim CA, Sugayama SM, Albano LM, Wagenfuhr J, Moyses RL, Gonzalez CH (2000) Cardiac findings in 31 patients with Noonan’s syndrome. Arq Bras Cardiol 75: 409–412CrossRefPubMed
2.
Zurück zum Zitat Burch M, Sharland M, Shinebourne E, Smith G, Patton M, McKenna W (1993) Cardiologic abnormalities in Noonan syndrome: phenotypic diagnosis and echocardiographic assessment of 118 patients. J Am Coll Cardiol 22: 1189–1192PubMed Burch M, Sharland M, Shinebourne E, Smith G, Patton M, McKenna W (1993) Cardiologic abnormalities in Noonan syndrome: phenotypic diagnosis and echocardiographic assessment of 118 patients. J Am Coll Cardiol 22: 1189–1192PubMed
3.
Zurück zum Zitat Fragale A, Tartaglia M, Wu J, Gelb BD (2004) Noonan syndrome-associated SHP2/PTPN11 mutants cause EGF-dependent prolonged Gab1 binding and sustained ERK2/MAPK1 activation. Hum Mutat 23: 267–277CrossRefPubMed Fragale A, Tartaglia M, Wu J, Gelb BD (2004) Noonan syndrome-associated SHP2/PTPN11 mutants cause EGF-dependent prolonged Gab1 binding and sustained ERK2/MAPK1 activation. Hum Mutat 23: 267–277CrossRefPubMed
4.
Zurück zum Zitat Hamada M, Shigematsu Y, Ikeda S, Hara Y, Okayama H, Kodama K, Ochi T, Hiwada K (1997) Class Ia antiarrhythmic drug cibenzoline: a new approach to the medical treatment of hypertrophic obstructive cardiomyopathy. Circulation 96: 1520–1524PubMed Hamada M, Shigematsu Y, Ikeda S, Hara Y, Okayama H, Kodama K, Ochi T, Hiwada K (1997) Class Ia antiarrhythmic drug cibenzoline: a new approach to the medical treatment of hypertrophic obstructive cardiomyopathy. Circulation 96: 1520–1524PubMed
5.
Zurück zum Zitat Hirsch HD, Gelband H, Garcia O, Gottlieb S, Tamer DM (1975) Rapidly progressive obstructive cardiomyopathy in infants with Noonan’s syndrome. Report of two cases. Circulation 52: 1161–1165PubMed Hirsch HD, Gelband H, Garcia O, Gottlieb S, Tamer DM (1975) Rapidly progressive obstructive cardiomyopathy in infants with Noonan’s syndrome. Report of two cases. Circulation 52: 1161–1165PubMed
6.
7.
Zurück zum Zitat Kalidas K, Shaw AC, Crosby AH, Newbury-Ecob R, Greenhalgh L, Temple IK, Law C, Patel A, Patton MA, Jeffery S (2005) Genetic heterogeneity in LEOPARD syndrome: two families with no mutations in PTPN11. J Hum Genet 50: 21–25CrossRefPubMed Kalidas K, Shaw AC, Crosby AH, Newbury-Ecob R, Greenhalgh L, Temple IK, Law C, Patel A, Patton MA, Jeffery S (2005) Genetic heterogeneity in LEOPARD syndrome: two families with no mutations in PTPN11. J Hum Genet 50: 21–25CrossRefPubMed
8.
Zurück zum Zitat Klinghoffer AR, Kazlauskas A (1995) Identification of a putative Syp substrate, the PDGFß receptor. J Biol Chem 270: 22208–22217CrossRefPubMed Klinghoffer AR, Kazlauskas A (1995) Identification of a putative Syp substrate, the PDGFß receptor. J Biol Chem 270: 22208–22217CrossRefPubMed
9.
Zurück zum Zitat Kosaki K, Suzuki T, Muroya K, Hasegawa T, Sato S, Matsuo N, Kosaki R, Nagai T, Hasegawa Y, Ogata T (2002) PTPN11 mutations in seven Japanese patients with Noonan syndrome. J Clin Endocrinol Metab 87: 3529–3533CrossRefPubMed Kosaki K, Suzuki T, Muroya K, Hasegawa T, Sato S, Matsuo N, Kosaki R, Nagai T, Hasegawa Y, Ogata T (2002) PTPN11 mutations in seven Japanese patients with Noonan syndrome. J Clin Endocrinol Metab 87: 3529–3533CrossRefPubMed
10.
Zurück zum Zitat Marino B, Digilio MC, Toscano A, Giannotti A, Dallapiccola B (1999) Congenital heart diseases in children with Noonan syndrome: an expanded cardiac spectrum with high prevalence of atrioventricular canal. J Pediatr 135: 703–706PubMed Marino B, Digilio MC, Toscano A, Giannotti A, Dallapiccola B (1999) Congenital heart diseases in children with Noonan syndrome: an expanded cardiac spectrum with high prevalence of atrioventricular canal. J Pediatr 135: 703–706PubMed
11.
Zurück zum Zitat Nakaoka Y, Nishida K, Fujio Y, Izumi M, Terai K, Oshima Y, Sugiyama S, Matsuda S, Koyasu S, Yamauchi-Takihara K, Hirano T, Kawase I, Hirota H (2003) Activation of gp130 transduces hypertrophic signal through interaction of scaffolding/docking protein Gab1 with tyrosine phosphatase SHP2 in cardiomyocytes. Circ Res 93: 221–2219CrossRefPubMed Nakaoka Y, Nishida K, Fujio Y, Izumi M, Terai K, Oshima Y, Sugiyama S, Matsuda S, Koyasu S, Yamauchi-Takihara K, Hirano T, Kawase I, Hirota H (2003) Activation of gp130 transduces hypertrophic signal through interaction of scaffolding/docking protein Gab1 with tyrosine phosphatase SHP2 in cardiomyocytes. Circ Res 93: 221–2219CrossRefPubMed
12.
Zurück zum Zitat Neel BG, Gu H, Pao L (2003) The ‘Shp’ing news: SH2 domain-containing tyrosine phosphatases in cell signaling. Trends Biochem Sci 28: 284–293CrossRefPubMed Neel BG, Gu H, Pao L (2003) The ‘Shp’ing news: SH2 domain-containing tyrosine phosphatases in cell signaling. Trends Biochem Sci 28: 284–293CrossRefPubMed
13.
Zurück zum Zitat Noonan J, O’Connor W (1996) Noonan syndrome: a clinical description emphasizing the cardiac findings. Acta Paediatr Jpn 38: 76–83PubMed Noonan J, O’Connor W (1996) Noonan syndrome: a clinical description emphasizing the cardiac findings. Acta Paediatr Jpn 38: 76–83PubMed
14.
Zurück zum Zitat Pawson T, Scott DJ (1997) Signaling through scaffold, anchoring, and adaptor proteins. Science 278: 2075–2080CrossRefPubMed Pawson T, Scott DJ (1997) Signaling through scaffold, anchoring, and adaptor proteins. Science 278: 2075–2080CrossRefPubMed
15.
Zurück zum Zitat Sarkozy A, Conti E, Seripa D, Digilio MC, Grifone N, Tandoi C, Fazio VM, Di Ciommo V, Marino B, Pizzuti A, Dallapiccola B (2003) Correlation between PTPN11 gene mutations and congenital heart defects in Noonan and LEOPARD syndromes. J Med Genet 40: 704–708CrossRefPubMed Sarkozy A, Conti E, Seripa D, Digilio MC, Grifone N, Tandoi C, Fazio VM, Di Ciommo V, Marino B, Pizzuti A, Dallapiccola B (2003) Correlation between PTPN11 gene mutations and congenital heart defects in Noonan and LEOPARD syndromes. J Med Genet 40: 704–708CrossRefPubMed
16.
Zurück zum Zitat Schaeper U, Gehring HN, Fuchs PK, Sachs M, Kempkes B, Birchmeier W (2000) Coupling of Gab1 to c-Met, Grb2, and Shp2 mediates biological responses. J Cell Biol 149: 1419–1432CrossRefPubMed Schaeper U, Gehring HN, Fuchs PK, Sachs M, Kempkes B, Birchmeier W (2000) Coupling of Gab1 to c-Met, Grb2, and Shp2 mediates biological responses. J Cell Biol 149: 1419–1432CrossRefPubMed
17.
Zurück zum Zitat Skinner JR, Manzoor A, Hayes AM, Joffe HS, Martin RP (1997) A regional study of presentation and outcome of hypertrophic cardiomyopathy in infants. Heart 77: 229–233PubMed Skinner JR, Manzoor A, Hayes AM, Joffe HS, Martin RP (1997) A regional study of presentation and outcome of hypertrophic cardiomyopathy in infants. Heart 77: 229–233PubMed
18.
Zurück zum Zitat 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 (2001) Mutations in PTPN11, encoding the protein tyrosine phosphatase SHP-2, cause Noonan syndrome. Nat Genet 29: 465–468CrossRefPubMed 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 (2001) Mutations in PTPN11, encoding the protein tyrosine phosphatase SHP-2, cause Noonan syndrome. Nat Genet 29: 465–468CrossRefPubMed
19.
Zurück zum Zitat Tartaglia M, Kalidas K, Shaw A, Song X, Musat DL, van der Burgt I, Brunner HG, Bertola DR, Crosby A, Ion A, Kucherlapati RS, Jeffery S, Patton MA, Gelb BD (2002) PTPN11 mutations in Noonan syndrome: molecular spectrum, genotype-phenotype correlation, and phenotypic heterogeneity. Am J Hum Genet 70: 1555–1563CrossRefPubMed Tartaglia M, Kalidas K, Shaw A, Song X, Musat DL, van der Burgt I, Brunner HG, Bertola DR, Crosby A, Ion A, Kucherlapati RS, Jeffery S, Patton MA, Gelb BD (2002) PTPN11 mutations in Noonan syndrome: molecular spectrum, genotype-phenotype correlation, and phenotypic heterogeneity. Am J Hum Genet 70: 1555–1563CrossRefPubMed
20.
Zurück zum Zitat Yoshida R, Hasegawa T, Hasegawa Y, Nagai T, Kinoshita E, Tanaka Y, Kanegane H, Ohyama K, Onishi T, Hanew K, Okuyama T, Horikawa R, Tanaka T, Ogata T (2004) Protein-tyrosine phosphatase, nonreceptor type 11 mutation analysis and clinical assessment in 45 patients with Noonan syndrome. J Clin Endocrinol Metab 89: 3359–3364CrossRefPubMed Yoshida R, Hasegawa T, Hasegawa Y, Nagai T, Kinoshita E, Tanaka Y, Kanegane H, Ohyama K, Onishi T, Hanew K, Okuyama T, Horikawa R, Tanaka T, Ogata T (2004) Protein-tyrosine phosphatase, nonreceptor type 11 mutation analysis and clinical assessment in 45 patients with Noonan syndrome. J Clin Endocrinol Metab 89: 3359–3364CrossRefPubMed
21.
Zurück zum Zitat Zenker M, Buheitel G, Rauch R, Koenig R, Bosse K, Kress W, Tietze HU, Doerr HG, Hofbeck M, Singer H, Reis A, Rauch A (2004) Genotype-phenotype correlations in Noonan syndrome. J Pediatr 144: 368–374CrossRefPubMed Zenker M, Buheitel G, Rauch R, Koenig R, Bosse K, Kress W, Tietze HU, Doerr HG, Hofbeck M, Singer H, Reis A, Rauch A (2004) Genotype-phenotype correlations in Noonan syndrome. J Pediatr 144: 368–374CrossRefPubMed
Metadaten
Titel
A novel mutation in the PTPN11 gene in a patient with Noonan syndrome and rapidly progressive hypertrophic cardiomyopathy
verfasst von
Kunihiko Takahashi
Shigetoyo Kogaki
Shunji Kurotobi
Sayaka Nasuno
Makiko Ohta
Hitomi Okabe
Kazuko Wada
Norio Sakai
Masako Taniike
Keiichi Ozono
Publikationsdatum
01.08.2005
Verlag
Springer-Verlag
Erschienen in
European Journal of Pediatrics / Ausgabe 8/2005
Print ISSN: 0340-6199
Elektronische ISSN: 1432-1076
DOI
https://doi.org/10.1007/s00431-005-1679-y

Weitere Artikel der Ausgabe 8/2005

European Journal of Pediatrics 8/2005 Zur Ausgabe

Update Pädiatrie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.