Genotype-phenotype correlations in MYCN-related Feingold syndrome
- 9 May 2008
- journal article
- research article
- Published by Hindawi Limited in Human Mutation
- Vol. 29 (9), 1125-1132
- https://doi.org/10.1002/humu.20750
Abstract
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, ΔMYCN. 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 ΔMYCN isoform, without a phenotypic effect. This suggests that mutations in only ΔMYCN 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. Hum Mutat 29(9), 1125–1132, 2008.This publication has 29 references indexed in Scilit:
- Expanding the clinical spectrum of MYCN‐related Feingold syndromeAmerican Journal of Medical Genetics Part A, 2006
- N-Mycand the cyclin-dependent kinase inhibitors p18Ink4cand p27Kip1coordinately regulate cerebellar developmentProceedings of the National Academy of Sciences of the United States of America, 2006
- Vertebral defects in a patient with Feingold syndromeClinical Dysmorphology, 2005
- Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomesGenome Research, 2005
- MYCN haploinsufficiency is associated with reduced brain size and intestinal atresias in Feingold syndromeNature Genetics, 2005
- Feingold syndrome: Clinical review and genetic mappingAmerican Journal of Medical Genetics Part A, 2003
- Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2−ΔΔCT MethodMethods, 2001
- A new mathematical model for relative quantification in real-time RT-PCRNucleic Acids Research, 2001
- Feingold syndrome – a cause of profound deafnessThe Journal of Laryngology & Otology, 1999
- Autosomal dominant inheritance of abnormalities of the hands and feet with short palpebral fissures, variable microcephaly with learning disability, and oesophageal/duodenal atresia.Journal of Medical Genetics, 1991