High resolution melting analysis for mutation detection for PTPN11 gene: applications of this method for diagnosis of Noonan syndrome.
BACKGROUND
Noonan syndrome (NS, OMIM 163950) is a relatively common autosomal dominant disorder and has significant phenotypic overlap with Costello Syndrome and cardio-facio-cutaneous syndrome. Molecular diagnosis is useful for differential diagnosis. PTPN11 gene mutation is the most common mutation associated with NS and hence is a suitable target for molecular diagnostics.


METHODS
High resolution melting (HRM) analysis was used for screening of PTPN11 mutations. Eleven DNA samples with 10 known PTPN11 mutations were used for HRM calibration. Said calibrations were then applied to mutation screening of a panel of 50 additional NS patients.


RESULTS
HRM analysis differentiated all of the 10 known mutations and identified 9 additional mutations from 10 patients in the blind study, which is in line with results obtained by sequencing.


CONCLUSIONS
HRM analysis is a rapid, reliable, and low-cost tool for detection of PTPN11 genetic variants.
Lo
Fu-Sung
FS
Division of Pediatric Endocrinology, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
Luo
Ji-Dung
JD
Lee
Yann-Jinn
YJ
Shu
San-Ging
SG
Kuo
Min-Tzu
MT
Chiou
Chiuan-Chian
CC
D004252:DNA Mutational Analysis / Q000379:methods*; D006801:Humans; D009154:Mutation; D009634:Noonan Syndrome / Q000175:diagnosis* / Q000235:genetics*; D009691:Nucleic Acid Denaturation; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11 / Q000235:genetics*; D013997:Time Factors
C516724:PTPN11 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11