Linkage of hereditary haemorrhagic telangiectasia to chromosome 9q34 and evidence for locus heterogeneity

Journal Article · Thu Sep 01 04:00:00 EDT 1994 · American Journal of Human Genetics

OSTI ID:134696

Breedveld, G J; Heutink, P ^[1]; Haitjema, T ^[2]

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1. Erasmus Univ., Rotterdam (Netherlands)
2. St. Antonium Hospital, Nieuwegein (Netherlands); and others

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disorder with unknown pathophysiology that is characterized by arteriovenous lesions and recurrent hemorrhage in virtually every organ. The prevalence of HHT ranges between 1-2 per 100,000 and 1 per 10,000 with almost complete penetrance by the age of 40 years. The mode of inheritance is autosomal dominant. Linkage of HHT to markers on chromosome 9q has recently been reported. In this study we present confirmation of this localization in three unrelated families of Dutch origin. A fourth family yielded evidence for non-linkage to this region. Heterogeneity analysis was performed and clearly demonstrated that HHT is a genetically heterogeneous disorder. We have rigorously investigated all patients in our four families by chest radiography, measurement of arterial oxygenation iv-DSA of the pulmonary circulation and iv-DSA of the cerebral circulation. In the family that is not linked to chromosome 9, considerably less pulmonary arteriovenous malformations (PAVM) were present. We conclude that HHT is a genetically heterogeneous disorder and our results indicate that the presence of PAVM may be more common in patients with a chromosome 9-linked form of HHT than in patients with the non-linked form. Linkage of HHT with a locus on chromosome 9q34 locus has now been reported in three independent studies. However, two studies report genetic heterogeneity. This will limit the applicability of linked DNA markers in small families for presymptomatic testing. Only extended pedigrees will be informative enough to determine whether or not the chromosome 9 locus is responsible for disease onset in the patient. The eventual isolation of the gene responsible for HHT on chromosome 9 will help to gain insight into the processes that take place in the development and remodelling of the vascular system.

• OSTI ID: 134696
• Report Number(s): CONF-941009--
• Journal Information: American Journal of Human Genetics, Journal Name: American Journal of Human Genetics Journal Issue: Suppl.3 Vol. 55; ISSN AJHGAG; ISSN 0002-9297
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
BIOLOGICAL MARKERS
CARDIOVASCULAR SYSTEM
DOMINANT MUTATIONS
GENES
GENETIC MAPPING
GENETICS
HEMIC DISEASES
HEREDITARY DISEASES
HUMAN CHROMOSOME 9
MALFORMATIONS
NETHERLANDS
PATIENTS
STATISTICS
TELANGIECTASIS