Genetic heterogeneity in hereditary hemorrhagic telangiectasia: Possible correlation with clinical phenotype

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

OSTI ID:134093

Papenberg, K A; Lennon, F; Helmbold, E A ^[1]

---

1. and others

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant generalized vascular dysplasia characterized by recurrent hemorrhage. Our initial linkage studies found an HHT gene to be localized to 9q3 in two large kindreds. In the present study, we have examined an additional five unrelated HHT families. The multipoint linkage analysis in this region resulted in a peak multipoint lod score of 13.03. Two additional proximal crossovers in affected individuals in one of these families have now further defined the candidate region on 9q3. In addition, significant evidence for heterogeneity of HHT found. The multipoint analysis supported the two-point studies with the odds of 3,000,000: 1 showing linkage and heterogeneity over linkage and homogeneity. Four of the seven families gave a posterior probability of > 99% of being of the linked type, while three families are unlinked to this region of 9q. The multipoint lod score using only the linked families is 21.70. Finally, a possible correlation in clinical phenotype between the 9q3-linked families and unlinked families is described. Although six of the seven families clearly meet the clinical criteria for HHT diagnosis, a significant absence of PAVMs is seen in all 9q3-unlinked families. This genetic heterogeneity and possible correlation to a clinical phenotype may have a significant impact on the clinical management and treatment of HHT patients.

• OSTI ID: 134093
• 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
CROSSING-OVER
DOMINANT MUTATIONS
GENES
GENETIC MAPPING
GENETICS
HEMORRHAGE
HEREDITARY DISEASES
HUMAN CHROMOSOME 9
PATIENTS
PHENOTYPE
STATISTICS
VASCULAR DISEASES