PMID- 18042262
OWN - NLM
STAT- MEDLINE
DCOM- 20080229
LR  - 20161124
IS  - 1399-0004 (Electronic)
IS  - 0009-9163 (Linking)
VI  - 73
IP  - 1
DP  - 2008 Jan
TI  - Mutation and phenotypic spectrum in patients with cardio-facio-cutaneous and 
      Costello syndrome.
PG  - 62-70
AB  - Cardio-facio-cutaneous (CFC) and Costello syndrome (CS) are congenital disorders 
      with a significant clinical overlap. The recent discovery of heterozygous 
      mutations in genes encoding components of the RAS-RAF-MAPK pathway in both CFC 
      and CS suggested a similar underlying pathogenesis of these two disorders. While 
      CFC is heterogeneous with mutations in BRAF, MAP2K1, MAP2K2 and KRAS, HRAS 
      alterations are almost exclusively associated with CS. We carried out a 
      comprehensive mutation analysis in 51 CFC-affected patients and 31 individuals 
      with CS. Twelve different BRAF alterations were found in twenty-four patients 
      with CFC (47.0%), two MAP2K1 mutations in five (9.8%) and two MAP2K2 sequence 
      variations in three CFC-affected individuals (5.9%), whereas three patients had a 
      KRAS alteration (5.9%). We identified four different missense mutations of HRAS 
      in twenty-eight cases with CS (90.3%), while KRAS mutations were detected in two 
      infants with a phenotype meeting criteria for CS (6.5%). In 14 informative 
      families, we traced the parental origin of HRAS alterations and demonstrated 
      inheritance of the mutated allele exclusively from the father, further confirming 
      a paternal bias in the parental origin of HRAS mutations in CS. Careful clinical 
      evaluation of patients with BRAF and MAP2K1/2 alterations revealed the presence 
      of slight phenotypic differences regarding craniofacial features in MAP2K1- and 
      MAP2K2-mutation positive individuals, suggesting possible genotype-phenotype 
      correlations.
FAU - Schulz, A L
AU  - Schulz AL
AD  - Institut fur Humangenetik, Universitatsklinikum Hamburg-Eppendorf, Hamburg, 
      Germany.
FAU - Albrecht, B
AU  - Albrecht B
FAU - Arici, C
AU  - Arici C
FAU - van der Burgt, I
AU  - van der Burgt I
FAU - Buske, A
AU  - Buske A
FAU - Gillessen-Kaesbach, G
AU  - Gillessen-Kaesbach G
FAU - Heller, R
AU  - Heller R
FAU - Horn, D
AU  - Horn D
FAU - Hubner, C A
AU  - Hubner CA
FAU - Korenke, G C
AU  - Korenke GC
FAU - Konig, R
AU  - Konig R
FAU - Kress, W
AU  - Kress W
FAU - Kruger, G
AU  - Kruger G
FAU - Meinecke, P
AU  - Meinecke P
FAU - Mucke, J
AU  - Mucke J
FAU - Plecko, B
AU  - Plecko B
FAU - Rossier, E
AU  - Rossier E
FAU - Schinzel, A
AU  - Schinzel A
FAU - Schulze, A
AU  - Schulze A
FAU - Seemanova, E
AU  - Seemanova E
FAU - Seidel, H
AU  - Seidel H
FAU - Spranger, S
AU  - Spranger S
FAU - Tuysuz, B
AU  - Tuysuz B
FAU - Uhrig, S
AU  - Uhrig S
FAU - Wieczorek, D
AU  - Wieczorek D
FAU - Kutsche, K
AU  - Kutsche K
FAU - Zenker, M
AU  - Zenker M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20071127
PL  - Denmark
TA  - Clin Genet
JT  - Clinical genetics
JID - 0253664
RN  - 0 (KRAS protein, human)
RN  - 0 (Proto-Oncogene Proteins)
RN  - EC 2.7.1.- (MAP2K2 protein, human)
RN  - EC 2.7.11.1 (BRAF protein, human)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins B-raf)
RN  - EC 2.7.12.2 (MAP Kinase Kinase 1)
RN  - EC 2.7.12.2 (MAP Kinase Kinase 2)
RN  - EC 2.7.12.2 (MAP2K1 protein, human)
RN  - EC 3.6.5.2 (Proto-Oncogene Proteins p21(ras))
RN  - EC 3.6.5.2 (ras Proteins)
SB  - IM
MH  - Abnormalities, Multiple/*genetics
MH  - Adult
MH  - Child
MH  - DNA Mutational Analysis
MH  - Developmental Disabilities
MH  - *Facies
MH  - Heart Defects, Congenital/*genetics
MH  - Humans
MH  - Intellectual Disability
MH  - MAP Kinase Kinase 1/genetics
MH  - MAP Kinase Kinase 2/genetics
MH  - *Mutation
MH  - Phenotype
MH  - Proto-Oncogene Proteins/genetics
MH  - Proto-Oncogene Proteins B-raf/genetics
MH  - Proto-Oncogene Proteins p21(ras)
MH  - Skin Abnormalities/*genetics
MH  - Syndrome
MH  - ras Proteins/genetics
EDAT- 2007/11/29 09:00
MHDA- 2008/03/01 09:00
CRDT- 2007/11/29 09:00
PHST- 2007/11/29 09:00 [pubmed]
PHST- 2008/03/01 09:00 [medline]
PHST- 2007/11/29 09:00 [entrez]
AID - CGE931 [pii]
AID - 10.1111/j.1399-0004.2007.00931.x [doi]
PST - ppublish
SO  - Clin Genet. 2008 Jan;73(1):62-70. doi: 10.1111/j.1399-0004.2007.00931.x. Epub 
      2007 Nov 27.