title: A fourth locus for hereditary hemorrhagic telangiectasia maps to chromosome 7.
abstract: Hereditary hemorrhagic telangiectasia (HHT) is a genetically and clinically heterogeneous multisystem vascular dysplasia. Mutations of the endoglin and ACVRL1 genes are known to cause HHT. However, existence of HHT families in which linkage to these genes has been excluded has suggested that other gene(s) can cause HHT in some families. Recently, a family was reported to be linked to chromosome 5q, the HHT3 locus. Here we report on linkage results on a family with classic features of HHT, albeit a less severe phenotype with regards to epistaxis and telangiectases, in which linkage to HHT1, HHT2, and HHT3 is ruled out. Whole genome linkage analysis and fine mapping results suggested a 7 Mb region on the short arm of chromosome 7 (7p14) between STR markers D7S2252 and D7S510. We obtained a maximum two point LOD score of 3.60 with the STR marker D7S817. This region was further confirmed by haplotype analysis. These findings suggest the presence of another gene causing HHT (HHT4). The features in this family that strongly suggest the presence of a hereditary, multisystem vascular dysplasia would be easily missed during the typical evaluation and management of a patient with an AVM. This family helps emphasize the need to obtain a very detailed, targeted medical and family history for even mild, infrequent but recurring nosebleed, subtle telangiectases. Further studies of the candidate region and the identification of the gene responsible for the vascular anomalies in this family will add to our understanding of vascular morphogenesis and related disorders.
authors.affiliation: Associated Regional and University Pathologists (ARUP), Institute of Clinical and Experimental Pathology, Salt Lake City, Utah 84108, USA. pinbayrak@yahoo.com
authors.forename: Pinar
authors.initials: P
authors.lastname: Bayrak-Toydemir
authors.forename: Jamie
authors.initials: J
authors.lastname: McDonald
authors.forename: Nurten
authors.initials: N
authors.lastname: Akarsu
authors.forename: Reha M
authors.initials: RM
authors.lastname: Toydemir
authors.forename: Fernanda
authors.initials: F
authors.lastname: Calderon
authors.forename: Timur
authors.initials: T
authors.lastname: Tuncali
authors.forename: Wei
authors.initials: W
authors.lastname: Tang
authors.forename: Franklin
authors.initials: F
authors.lastname: Miller
authors.forename: Rong
authors.initials: R
authors.lastname: Mao
mesh_terms: D030301:Activin Receptors, Type II / Q000235:genetics; D000328:Adult; D001483:Base Sequence; D002874:Chromosome Mapping; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics*; D005260:Female; D006801:Humans; D008126:Lod Score; D018895:Microsatellite Repeats / Q000235:genetics; D008969:Molecular Sequence Data; D010375:Pedigree; D010641:Phenotype; D017422:Sequence Analysis, DNA; D013683:Telangiectasia, Hereditary Hemorrhagic / Q000235:genetics* / Q000473:pathology
chemical_list: C425364:ACVRL1 protein, human; D030301:Activin Receptors, Type II