Carney complex, a familial multiple neoplasia and lentiginosis syndrome: Analysis of 11 kindreds and linkage to the short arm of chromosome 2

Constantine A. Stratakis, J. Aidan Carney, Jing Ping Lin, Dimitris A. Papanicolaou, Michael Karl, Daniel L. Kastner, Elon Pras, George P. Chrousos

Research output: Contribution to journalArticlepeer-review

Abstract

Carney complex is an autosomal dominant syndrome characterized by multiple neoplasias, including myxomas at various sites and endocrine tumors, and lentiginosis. The genetic defect(s) responsible for the complex remain(s) unknown. We studied 101 subjects, including 51 affected members, from 11 North American kindreds with Carney complex. Blood samples were collected from patients and their family members. Hospital records, photographs, and tissue specimens of deceased individuals were reviewed. DNA was extracted from blood samples, patient-derived cell lines, and/or paraffin-embedded tissues. Linkage analysis was performed with highly polymorphic microsatellite markers, distributed over areas of the human genome harboring the most likely candidate genes. The most prevalent clinical manifestation in patients with Carney complex was spotty skin pigmentation, similar to that observed in Peutz-Jeghers and other lentiginosis syndromes. Skin and cardiac myxomas, Cushing syndrome, and acromegaly were present in 62, 30, 31, and 8 percent of the patients, respectively. Linkage was obtained for three markers on the short arm of chromosome 2 (2p16), with a maximum two-point lod score of 5.97 at Θ = 0.03 for the marker CA-2 (odds in favor of linkage 106:1). The flanking markers CA7 and D2S378 defined a region of ~ 6.4 cM that is likely to contain the gene(s) associated with Carney complex. Candidate genes in the proximity, including the propiomelanocortin and the DNA-mismatch repair hMSH2 genes, were excluded. We conclude that the genetic defect(s) responsible for Carney complex map(s) to the short arm of chromosome 2 (2p16). This region has exhibited cytogenetic aberrations in atrial myxomas associated with the complex, and has been characterized by microsatellite instability in human neoplasias.

Original languageEnglish
Pages (from-to)699-705
Number of pages7
JournalJournal of Clinical Investigation
Volume97
Issue number3
DOIs
StatePublished - 1 Feb 1996
Externally publishedYes

Keywords

  • Carney complex
  • chromosome 2p
  • linkage
  • multiple endocrine neoplasia (MEN)
  • myxomas

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