Epistatic interactions with a common hypomorphic RET allele in syndromic Hirschsprung disease

@article{DePontual2007EpistaticIW,
  title={Epistatic interactions with a common hypomorphic RET allele in syndromic Hirschsprung disease},
  author={Loïc De Pontual and Anna Pelet and Mathieu Cl{\'e}ment-Ziza and Delphine Trochet and S. E. Antonarakis and Tania Atti{\'e}-Bitach and Philip Beales and Jean Louis Blouin and Florence Dastot‐Le Moal and H{\'e}l{\`e}ne Dollfus and Michel Goossens and Nicholas Katsanis and Renaud Laurian Touraine and J. Feingold and Arnold Munnich and Stanislas Lyonnet and Jeanne Amiel},
  journal={Human Mutation},
  year={2007},
  volume={28}
}
Hirschsprung disease (HSCR) stands as a model for genetic dissection of complex diseases. In this model, a major gene, RET, is involved in most if not all cases of isolated (i.e., nonsyndromic) HSCR, in conjunction with other autosomal susceptibility loci under a multiplicative model. HSCR susceptibility alleles can harbor either heterozygous coding sequence mutations or, more frequently, a polymorphism within intron 1, leading to a hypomorphic RET allele. On the other hand, about 30% of HSCR… 
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A role for CNVs in HSCR is suggested and the role of variation in regulatory sequences is emphasizes and a much larger study will be necessary both for replication and for identifying the full spectrum of small CNV effects.
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Waardenburg syndrome type IIE in a Japanese patient caused by a novel non‐frame‐shift duplication mutation in the SOX10 gene
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The ret proto-oncogene (RET), a receptor tyrosine kinase has emerged as a central player in the development of HSCR, most frequently modified in effect by the contributions of risk alleles at other loci.
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