Document Detail


Genotype-phenotype correlations in MYCN-related Feingold syndrome.
MedLine Citation:
PMID:  18470948     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Feingold syndrome (FS) is the most frequent cause of familial syndromic gastrointestinal atresia and follows autosomal dominant inheritance. FS is caused by germline mutations in or deletions of the MYCN gene. Previously, 12 different heterozygous MYCN mutations and two deletions containing multiple genes including MYCN were described. All these mutations result in haploinsufficiency of both the canonical MYCN protein and the shorter isoform, DeltaMYCN. We report 11 novel mutations including seven mutations in exon 2 that result in a premature termination codon (PTC) in the long MYCN transcript. Moreover, we have identified a PTC in exon 1 that only affects the DeltaMYCN isoform, without a phenotypic effect. This suggests that mutations in only DeltaMYCN do not contribute to the FS. Additionally, we found three novel deletions encompassing MYCN. Together with our previous report we now have a total of four missense mutations in the DNA binding domain, 19 PTCs of which six render the transcript subject to nonsense-mediated decay (NMD), and five larger deletions in a total of 77 patients. We have reviewed the clinical features of these patients, and found that digital anomalies, e.g., brachymesophalangy and toe syndactyly, are the most consistent features, present in 100% and 97% of the patients, respectively. Small head circumference was present in 89% of the cases. Gastrointestinal atresia remains the most important major congenital anomaly (55%), but cardiac and renal anomalies are also frequent. We suggest that the presence of brachymesophalangy and toe syndactyly in combination with microcephaly is enough to justify MYCN analysis.
Authors:
Carlo L M Marcelis; Frans A Hol; Gail E Graham; Paul N M A Rieu; Richard Kellermayer; Rowdy P P Meijer; Dorien Lugtenberg; Hans Scheffer; Hans van Bokhoven; Han G Brunner; Arjan P M de Brouwer
Related Documents :
2167308 - Structure-function studies of adenine nucleotide transport in mitochondria. i. construc...
9485068 - Increased abeta42(43) from cell lines expressing presenilin 1 mutations.
6248868 - Recombination genes on the escherichia coli sex factor specific for transposable elements.
3927158 - Mutational and pseudomutational effects of 5-bromodeoxyuridine in human lymphoblasts.
7069658 - Morphological selection of human spermatozoa in vivo and in vitro.
9339898 - Characterization of four yeast artificial chromosome clones mapped to human chromosome ...
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Human mutation     Volume:  29     ISSN:  1098-1004     ISO Abbreviation:  Hum. Mutat.     Publication Date:  2008 Sep 
Date Detail:
Created Date:  2008-09-02     Completed Date:  2008-11-24     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9215429     Medline TA:  Hum Mutat     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1125-32     Citation Subset:  IM    
Affiliation:
Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands. c.marcelis@antrg.umcn.nl
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Abnormalities, Multiple / genetics*
Digestive System Abnormalities / genetics
Family Health
Genes, Dominant
Genotype
Intestinal Atresia / genetics*
Microcephaly / genetics
Mutation*
Nuclear Proteins / genetics*
Oncogene Proteins / genetics*
Phenotype
Syndactyly / genetics
Syndrome
Toes / abnormalities
Chemical
Reg. No./Substance:
0/MYCN protein, human; 0/Nuclear Proteins; 0/Oncogene Proteins

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Dynamic nature of the proximal AZFc region of the human Y chromosome: multiple independent deletion ...
Next Document:  Dry-reagent disposable biosensor for visual genotyping of single nucleotide polymorphisms by oligonu...