Two cases of Noonan syndrome with severe respiratory and gastroenteral involvement and the SOS1 mutation F623I.
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Two cases of Noonan syndrome with severe respiratory and gastroenteral involvement and the SOS1 mutation F623I. / Fabretto, Antonella; Kutsche, Kerstin; Harmsen, May-Britt; Demarini, Sergio; Gasparini, Paolo; Fertz, Maria Cristina; Zenker, Martin.
In: EUR J MED GENET, Vol. 53, No. 5, 5, 2010, p. 322-324.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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T1 - Two cases of Noonan syndrome with severe respiratory and gastroenteral involvement and the SOS1 mutation F623I.
AU - Fabretto, Antonella
AU - Kutsche, Kerstin
AU - Harmsen, May-Britt
AU - Demarini, Sergio
AU - Gasparini, Paolo
AU - Fertz, Maria Cristina
AU - Zenker, Martin
PY - 2010
Y1 - 2010
N2 - Noonan syndrome (NS) is an autosomal dominant, inherited disorder characterized by facial dysmorphism, congenital heart defects, and reduced postnatal growth. Dysregulated RAS-MAPK signalling is the common molecular basis for NS, a genetically heterogeneous disease. Germline mutations in genes encoding small GTPases of the RAS family (KRAS and NRAS), modulators of RAS function (PTPN11, SOS1 and SHOC2) or downstream signal transducers (RAF1) are causative for NS. SOS1 is the second major gene for NS after PTPN11. Compared to patients with mutations in other genes, SOS1 mutation-positive individuals in general tend to have a more favorable outcome, with less short stature and cognitive impairment. We describe two unrelated patients with NS carrying the same heterozygous SOS1 missense mutation (c.1867T > A/p.F623I). The phenotype of both patients is remarkable as they show uncommon clinical features such as pulmonary lymphangiectasis, congenital pleural effusions, severe feeding problems, and laryngomalacia. These findings may be related to the specific mutation present in our two patients, or be part of the SOS1 phenotype. Detailed clinical assessment of large cohorts of patients with NS and SOS1 mutation is required to clarify this initial observation.
AB - Noonan syndrome (NS) is an autosomal dominant, inherited disorder characterized by facial dysmorphism, congenital heart defects, and reduced postnatal growth. Dysregulated RAS-MAPK signalling is the common molecular basis for NS, a genetically heterogeneous disease. Germline mutations in genes encoding small GTPases of the RAS family (KRAS and NRAS), modulators of RAS function (PTPN11, SOS1 and SHOC2) or downstream signal transducers (RAF1) are causative for NS. SOS1 is the second major gene for NS after PTPN11. Compared to patients with mutations in other genes, SOS1 mutation-positive individuals in general tend to have a more favorable outcome, with less short stature and cognitive impairment. We describe two unrelated patients with NS carrying the same heterozygous SOS1 missense mutation (c.1867T > A/p.F623I). The phenotype of both patients is remarkable as they show uncommon clinical features such as pulmonary lymphangiectasis, congenital pleural effusions, severe feeding problems, and laryngomalacia. These findings may be related to the specific mutation present in our two patients, or be part of the SOS1 phenotype. Detailed clinical assessment of large cohorts of patients with NS and SOS1 mutation is required to clarify this initial observation.
M3 - SCORING: Zeitschriftenaufsatz
VL - 53
SP - 322
EP - 324
JO - EUR J MED GENET
JF - EUR J MED GENET
SN - 1769-7212
IS - 5
M1 - 5
ER -
