Linkage of Marfan syndrome and a phenotypically related disorder to two different fibrillin genes

Brendan Lee, Maurice Godfrey, Emilia Vitale, Hisae Hori, Marie Geneviéve Mattei, Mansoor Sarfarazi, Petros Tsipouras, Francesco Ramirez, David W. Hollister

Research output: Contribution to journalArticlepeer-review

612 Scopus citations


MARFAN syndrome (MFS), one of the most common genetic disorders of connective tissue, is characterized by skeletal, cardiovascular and ocular abnormalities1. The incidence of the disease is about 1 in 20,000, with life expectancy severely reduced because of cardiovascular complications. As the underlying defect is unknown, MFS diagnosis is based solely on clinical criteria. Certain phenotypic features of MFS are also shared by other conditions, which may be genetically distinct entities although part of a clinical continuum. Immunohistochemical studies have implicated fibrillin, a major component of elastin-associated microfibrils2, in MFS aetiology3, 4. Genetic linkage analysis with random probes has independently localized the MFS locus to chromosome 15 (refs 5-7). Here we report that these two experimental approaches converge with the cloning and mapping of the fibrillin gene to chromosome 15ql5-21, and with the establishment of linkage to MFS. We also isolated a second fibrillin gene and mapped it to chromosome 5q23-31. We linked this novel gene to a condition, congenital contractual arachnodactyly, that shares some of the features of MFS1. Thus, the cosegregation of two related genes with two related syndromes implies that fibrillin mutations are likely to be responsible for different MFS phenotypes.

Original languageEnglish (US)
Pages (from-to)330-334
Number of pages5
Issue number6333
StatePublished - 1991

ASJC Scopus subject areas

  • General


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