Mutmainah, Iffa and Yntema, Helger and Faradz, Sultana MH (2015) MOLECULAR ANALYSIS OF SUSPECTED INDONESIAN NOONAN SYNDROME. Masters thesis, Universitas Diponegoro.

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Abstract

Background: Noonan syndrome (NS) is a genetic disorder characterized by dysmorphic facial features, congenital heart defects, and short stature. NS is previously known as pseudo Turner syndrome (TS) due to their phenotypic similarity. However, unlike TS, NS is non-chromosomal disorder and present in both males and females. Several genes involved in RAS-MAPK pathway found to be mutated in NS and sequencing was performed in order to find the mutation in those genes. Methods: Eight Turner phenotype patients with normal karyotype were included in this study. Clinical appearances were then compared to NS scoring system. DNA was sequenced by automated ion semiconductor sequencing for the four most common NS genes; PTPN11, SOS1, KRAS, and RAF1. The data was subsequently analyzed using Sequence pilot software. In silico prediction programs were used to predict the pathogenic effect of the genetic variants and classified according to existing guideline. Result: Three out of eight patients consider had NS face. One patient, who showed cardinal symptoms of NS, carried mutation of PTPN11 gene: an AC transition at position 317 in exon 3 indicating an Asp106Ala substitution. Other variants found in SOS1, KRAS, and RAF1 were classified either polymorphism or unlikely to be pathogenic. The remaining five patients considered as not having NS face. Conclusion: The molecular analysis in this study revealed NS in one out of eight Turner phenotype patients with normal karyotype. No pathogenic variant found in other patients may indicate that there is either a novel unidentified gene for NS or the patients have another disorder and not NS.
Keyword: Noonan syndrome, PTPN11, SOS1, KRAS, RAF1, ion semiconductor sequencing

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