2010年8月
Comprehensive genetic analysis of overlapping syndromes of RAS/RAF/MEK/ERK pathway
PEDIATRICS INTERNATIONAL
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- 巻
- 52
- 号
- 4
- 開始ページ
- 557
- 終了ページ
- 562
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1111/j.1442-200X.2009.03020.x
- 出版者・発行元
- WILEY-BLACKWELL
Background:
Germline mutations in several members of RAS/RAF/MEK/ERK pathway cause clinically similar genetic disorders, including Noonan syndrome (NS), Costello syndrome (CS) and cardio-facio-cutaneous syndrome (CFC). Each of these syndromes has a wide spectrum of molecular etiology. The aim of the present study was to conduct a comprehensive genetic analysis of RAS/RAF/MEK/ERK pathway in these syndromes.
Methods:
Three patients with NS and two patients with CS/CFC were examined. Peripheral blood samples were collected from all patients as well as from 100 healthy Japanese volunteers. The protein phosphatase, non-receptor type II (PTPN11), KRAS, HRAS, NRAS, BRAF, RAF1, Son of Sevenless (SOS1) and MEK1genes were analyzed.
Results:
In a patient with a severe Noonan phenotype, a rare PTPN11 mutation was detected: A to G transition at position 172, causing an N58D substitution within the N-SH2 domain. In a CS/CFC patient no HRAS mutations were found, but a novel SOS1 missense mutation was found: A to G transition at position 473, causing a T158A substitution within domain of histone-like fold (HF).
Conclusions:
A case mimicking CS with SOS1 T158A substitution, which has not been reported previously in CS, revealed the complex relationship between the genotype and phenotype of overlapping syndromes of the RAS/RAF/MEK/ERK pathway.
Germline mutations in several members of RAS/RAF/MEK/ERK pathway cause clinically similar genetic disorders, including Noonan syndrome (NS), Costello syndrome (CS) and cardio-facio-cutaneous syndrome (CFC). Each of these syndromes has a wide spectrum of molecular etiology. The aim of the present study was to conduct a comprehensive genetic analysis of RAS/RAF/MEK/ERK pathway in these syndromes.
Methods:
Three patients with NS and two patients with CS/CFC were examined. Peripheral blood samples were collected from all patients as well as from 100 healthy Japanese volunteers. The protein phosphatase, non-receptor type II (PTPN11), KRAS, HRAS, NRAS, BRAF, RAF1, Son of Sevenless (SOS1) and MEK1genes were analyzed.
Results:
In a patient with a severe Noonan phenotype, a rare PTPN11 mutation was detected: A to G transition at position 172, causing an N58D substitution within the N-SH2 domain. In a CS/CFC patient no HRAS mutations were found, but a novel SOS1 missense mutation was found: A to G transition at position 473, causing a T158A substitution within domain of histone-like fold (HF).
Conclusions:
A case mimicking CS with SOS1 T158A substitution, which has not been reported previously in CS, revealed the complex relationship between the genotype and phenotype of overlapping syndromes of the RAS/RAF/MEK/ERK pathway.
- リンク情報
- ID情報
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- DOI : 10.1111/j.1442-200X.2009.03020.x
- ISSN : 1328-8067
- PubMed ID : 20030748
- Web of Science ID : WOS:000280998900026