Abstract
Objectives
To test for PTPN11 mutations in clinically diagnosed cases of Noonan syndrome.
Methods
17 individuals with clinical diagnosis of Noonan syndrome were included in the study. Sanger sequencing of all the 15 exons of PTPN11 was done. A genotype-phenotype correlation was attempted.
Results
Mutation in PTPN11 was detected in 11 out of 17 (64.7 %) patients with Noonan syndrome; 72% had mutation in exon 3 and 27 % had mutation in exon 13.
Conclusion
PTPN11 mutation accounts for 64.7% of cases with clinical features of Noonan syndrome in India. Majority of the mutations are in exon 3 and exon 13 of PTPN11, making them the hotspots in Indian population.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Noonan JA. Hypertelorism with Turner phenotype. A new syndrome with associated congenital heart disease. Am J Dis Child.1968;16:373–80.
Nora JJ, Nora AH, Sinha AK, Spangler RD, Lubs HA. The Ullrich-Noonan syndrome (Turner phenotype). Am J Dis Child. 1974;127:48–55.
Tartaglia M, Mehler EL, Goldberg R, Zampino G, Brunner HG, Kremer H, et al. Mutations in PTPN11, encoding the protein tyrosine phosphatise SHP-2, cause Noonan syndrome. Nat Genet. 2001;29:465–8.
Tartaglia M, Kalidas K, Shaw A, Song X, Musat DL, van der Burgt I, et al. PTPN11 mutations in Noonan syndrome: molecular spectrum, genotype-phenotype correlation, and phenotypic heterogeneity. Am J Hum Genet. 2002; 70:1555–63.
Roberts AE, Araki T, Swanson KD, Montgomery KT, Schiripo TA, Joshi VA, et al. Germline gain-of-function mutations in SOS1 cause Noonan syndrome. Nat Genet. 2007;39:70–4.
Pandit B, Sarkozy A, Pennacchio LA, Carta C, Oishi K, Martinelli S, et al. Gain-of-function RAF1 mutations cause Noonan and LEOPARD syndromes with hypertrophic cardiomyopathy. Nat Genet. 2007;39:1007–12.
Razzaque MA, Nishizawa T, Komoike Y, Yagi H, Furutani M, Amo R, et al.Germline gain-of-function mutations in RAF1 cause Noonan syndrome. Nat Genet. 2007;39:1013.
Aoki Y, Niihori T, Banjo T, Okamoto N, Mizuno S, Kurosawa K, et al. Gain-of function mutations in RIT1 cause Noonan syndrome, a RAS/MAPK pathway syndrome. Am J Hum Genet. 2013; 93:173–80.
Van der Burgt I. Noonan syndrome. Orphanet J Rare Dis. 2007;2:4.
Romano AA, Allanson JE, Dahlgren J, Gelb BD, Hall B, Pierpont ME, et al. Noonan syndrome: Clinical features, diagnosis, and management guidelines. Pediatrics. 2010; 26:746–59.
Tartaglia M, Gelb BD, Zenker M. Noonan syndrome and clinically related disorders. Best Pract Res Clin Endocrinol Metab. 2011;25:161–79.
Sarkozy A, Conti E, Seripa D, Digilio MC, Grifone N, Tandoi C, et al. Correlation between PTPN11 gene mutations and congenital heart defects in Noonan and LEOPARD syndromes. J Med Genet. 2003;40:704–8.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Narayanan, D.L., Pandey, H., Moirangthem, A. et al. Hotspots in PTPN11 gene among Indian children with Noonan syndrome. Indian Pediatr 54, 638–640 (2017). https://doi.org/10.1007/s13312-017-1125-z
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s13312-017-1125-z