Congenital central hypoventilation syndrome: Mutation analysis of the receptor tyrosine kinase ret

Stacey Bolk, Misha Angrist, Stuart Schwartz, Jean M. Silvestri, Debra E. Weese-Mayer*, Araviada Chakravarti

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

46 Scopus citations


Congenital central hypoventilation syndrome (CCHS) usually occurs as an isolated phenotype. However, 16% of the index cases are also affected with Hirschsprung disease (HSCR). Complex segregation analysis suggests that CCHS is familial and has the same inheritance pattern with or without HSCR. We postulate that alteration of normal function of the receptor tyrosine kinase, RET, may contribute to CCHS based on RET's expression pattern and the identification of RET mutations in HSCR patients. To further explore the nature of the inheritance of CCHS, we have undertaken two main routes of investigation: cytogenetic analysis and mutation detection. Cytogenetic analysis of metaphase chromosomes showed normal karyotypes in 13 of the 14 evaluated index cases; one index case carried a familial pericentric inversion on chromosome 2. Mutation analysis showed no sequence changes unique to index cases, as compared to control individuals, and as studied by single strand conformational polymorphism (SSCP) analysis of the coding region of RET. We conclude that point mutations in the RET coding region cannot account for a substantial fraction of CCHS in this patient population, and that other candidate genes involved in neural crest cell differentiation and development must be considered.

Original languageEnglish (US)
Pages (from-to)603-609
Number of pages7
JournalAmerican Journal of Medical Genetics, Part C: Seminars in Medical Genetics
Issue number4
StatePublished - Jun 28 1996


  • Congenital central hypoventilation syndrome
  • Hirschsprung disease
  • Mutation detection
  • RET receptor tyrosine kinase

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics


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