Congenital central hypoventilation syndrome: mutation analysis of the receptor tyrosine kinase RET.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Bolk, S; Angrist, M; Schwartz, S; Silvestri, JM; Weese-Mayer, DE; Chakravarti, A

Published Date

  • June 1996

Published In

Volume / Issue

  • 63 / 4

Start / End Page

  • 603 - 609

PubMed ID

  • 8826440

Electronic International Standard Serial Number (EISSN)

  • 1096-8628

International Standard Serial Number (ISSN)

  • 0148-7299

Digital Object Identifier (DOI)

  • 10.1002/(sici)1096-8628(19960628)63:4<603::aid-ajmg14>;2-m


  • eng