Sign up to save your podcasts
Or
Share SOS1 is the second most common Noonan gene but plays no major role in cardio-facio-cutaneous syndrome.
Share to email
Share to Facebook
Share to X
Share to email
Share to Facebook
Share to X
Or
SOS1 is the second most common Noonan gene but plays no major role in cardio-facio-cutaneous syndrome.
Background: Heterozygous gain-of-function mutations in various
genes encoding proteins of the Ras-MAPK signalling
cascade have been identified as the genetic basis of Noonan
syndrome (NS) and cardio-facio-cutaneous syndrome (CFCS).
Mutations of SOS1, the gene encoding a guanine nucleotide
exchange factor for Ras, have been the most recent discoveries
in patients with NS, but this gene has not been studied in
patients with CFCS.
Methods and results: We investigated SOS1 in a large cohort
of patients with disorders of the NS–CFCS spectrum, who had
previously tested negative for mutations in PTPN11, KRAS,
BRAF, MEK1 and MEK2. Missense mutations of SOS1 were
discovered in 28% of patients with NS. In contrast, none of the
patients classified as having CFCS was found to carry a
pathogenic sequence change in this gene.
Conclusion: We have confirmed SOS1 as the second major
gene for NS. Patients carrying mutations in this gene have a
distinctive phenotype with frequent ectodermal anomalies such
as keratosis pilaris and curly hair. However, the clinical picture
associated with SOS1 mutations is different from that of CFCS.
These findings corroborate that, despite being caused by gainof-
function mutations in molecules belonging to the same
pathway, NS and CFCS scarcely overlap genotypically.
View all episodes
By Ludwig-Maximilians-Universität MünchenBackground: Heterozygous gain-of-function mutations in various
genes encoding proteins of the Ras-MAPK signalling
cascade have been identified as the genetic basis of Noonan
syndrome (NS) and cardio-facio-cutaneous syndrome (CFCS).
Mutations of SOS1, the gene encoding a guanine nucleotide
exchange factor for Ras, have been the most recent discoveries
in patients with NS, but this gene has not been studied in
patients with CFCS.
Methods and results: We investigated SOS1 in a large cohort
of patients with disorders of the NS–CFCS spectrum, who had
previously tested negative for mutations in PTPN11, KRAS,
BRAF, MEK1 and MEK2. Missense mutations of SOS1 were
discovered in 28% of patients with NS. In contrast, none of the
patients classified as having CFCS was found to carry a
pathogenic sequence change in this gene.
Conclusion: We have confirmed SOS1 as the second major
gene for NS. Patients carrying mutations in this gene have a
distinctive phenotype with frequent ectodermal anomalies such
as keratosis pilaris and curly hair. However, the clinical picture
associated with SOS1 mutations is different from that of CFCS.
These findings corroborate that, despite being caused by gainof-
function mutations in molecules belonging to the same
pathway, NS and CFCS scarcely overlap genotypically.
More shows like Medizin - Open Access LMU - Teil 14/22
View all
Einführung in die Ethnologie
0 Listeners
Theoretical Physics Schools (ASC)
2 Listeners
MCMP – Mathematical Philosophy (Archive 2011/12)
6 Listeners
Hegel lectures by Robert Brandom, LMU Munich
6 Listeners
MCMP – Metaphysics and Philosophy of Language
2 Listeners
MCMP – Philosophy of Science
1 Listeners
MCMP – Philosophy of Physics
3 Listeners
Sommerfeld Lecture Series (ASC)
0 Listeners
Medizin - Open Access LMU - Teil 12/22
0 Listeners
Women Thinkers in Antiquity and the Middle Ages - SD
0 Listeners