A third locus for hereditary haemorrhagic telangiectasia maps to chromosome 12q

Vincent, P.; Plauchu, Henri; Hazan, Jamilé; Fauré, Sabine; Weissenbach, Jean; Godet, Jacqueline

doi:10.1093/hmg/4.5.945

Cited by 125 publications

(69 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Two original assignments of the HHT2 locus were given, one between D12S339 and D12S359 17 and the other in a neighbouring interval between D12S345 and D12S339 18 ( fig 4A). The latter was revised on subsequent analyses, and the ALK-1 gene is now known to lie in the 4 cM interval between D12S347 and D12S359, most probably in the 1 cM interval between D12S347 and D12S368.…”

Section: Exclusion Of Alk-1mentioning

confidence: 99%

A hereditary haemorrhagic telangiectasia family with pulmonary involvement is unlinked to the known HHT genes, endoglin and ALK-1

Wallace

Shovlin²

2000

Thorax

View full text Add to dashboard Cite

Methods-Family members were assessed clinically to assign HHT disease status and were screened for PAVMs. DNA was extracted from blood obtained from 20 individuals of known disease status. Short tandem repeat polymorphic markers spanning the intervals containing the endoglin and ALK-1 genes were amplified by the polymerase chain reaction using 33 P-labelled oligonucleotide primers, separated by denaturing polyacrylamide gel electrophoresis (PAGE), and the resultant autoradiographs were examined for allele sizes. Linkage analyses were performed using MLINK and GENE-HUNTER. Results-Twelve members spanning four generations were aVected with HHT. Two had proven PAVMs, one with a classical appearance, the other exhibiting microscopic PAVMs exacerbated by pregnancy. Two point lod and multipoint lod scores significantly excluded linkage to endoglin and ALK-1 in this pedigree. Conclusions-This study confirms the existence of a third HHT locus that accounts for disease in some HHT patients with pulmonary involvement. (Thorax 2000;55:685-690)

show abstract

Section: Exclusion Of Alk-1mentioning

confidence: 99%

A hereditary haemorrhagic telangiectasia family with pulmonary involvement is unlinked to the known HHT genes, endoglin and ALK-1

Wallace

Shovlin²

2000

Thorax

View full text Add to dashboard Cite

show abstract

“…Endoglin (CD105), which was assigned to this region previously (11), was defined as the mutated gene, and is referred to as HHT1 (12). A second locus (HHT2) mapping to chromosome 12q was discovered and shown to be the activin receptor-like kinase 1 (ALK1) (13)(14)(15). It is postulated that at least one more locus is involved in HHT that is more predominantly associated with liver AVM (16).…”

Section: Introductionmentioning

confidence: 99%

Mutant endoglin in hereditary hemorrhagic telangiectasia type 1 is transiently expressed intracellularly and is not a dominant negative.

Pece¹,

Vera²,

Cymerman³

et al. 1997

J. Clin. Invest.

150

131

View full text Add to dashboard Cite

Endoglin (CD105), a component of the TGF-␤ 1 receptor complex, is the target gene for the dominantly inherited vascular disorder hereditary hemorrhagic telangiectasia type 1 (HHT1). We have identified a novel endoglin splice site mutation, leading to an in-frame deletion of exon 3, in a newborn from a family with HHT. Expression of normal and mutant endoglin proteins was analyzed in umbilical vein endothelial cells from this baby and in activated monocytes from the affected father. In both samples, only normal dimeric endoglin (160 kD) was observed at the cell surface, at 50% of control levels. Despite an intact transmembrane region, mutant protein was only detectable by metabolic labeling, as an intracellular homodimer of 130 kD. In monocytes from three clinically affected HHT1 patients, with known mutations creating premature stop codons in exons 8 and 10, surface endoglin was also reduced by half and no mutant was detected. Overexpression into COS-1 cells of endoglin cDNA truncated in exons 7 and 11, revealed their intracellular expression, inability to be secreted and to form heterodimers at the cell surface. These results indicate that mutated forms of endoglin are transiently expressed intracellularly and not likely to act as dominant negative proteins, as proposed previously. A reduction in the level of functional endoglin is thus involved in the generation of HHT1, and associated arteriovenous malformations. ( J. Clin. Invest. 1997. 100:2568-2579.)

show abstract

“…1,2 Chromosomes 9q and 12q have been implicated in the inheritance of this disease. [3][4][5][6][7] A family history of HHT, although not required to make the diagnosis, is almost universally present. The vascular malformations of HHT may occur in multiple organs, including the lung, liver, kidney, and brain.…”

mentioning

confidence: 99%

Cerebrovascular Manifestations in 321 Cases of Hereditary Hemorrhagic Telangiectasia

Maher¹,

Piepgras²,

Brown³

et al. 2001

Stroke

213

104

View full text Add to dashboard Cite

Background and Purpose-Patients with hereditary hemorrhagic telangiectasia (HHT) are at risk for developing cerebral vascular malformations and pulmonary arteriovenous fistulae. We assessed the risk of neurological dysfunction from these malformations and fistulae. Methods-Three hundred twenty-one consecutive patients with HHT seen at a single institution over a 20-year period were studied. Any evidence of prior neurological symptoms or presence of an intracranial vascular malformation was recorded. All cases of possible cerebral arteriovenous malformation were confirmed by conventional arteriography. Results-Twelve patients (3.7%) had a history of cerebral vascular malformations. Ten patients had arteriovenous malformations, 1 had a dural arteriovenous fistula, and 1 had a cavernous malformation. Seven patients (2.1%) presented with intracranial hemorrhage, 2 presented with seizures alone, and 3 were discovered incidentally. The average age at the time of symptomatic intracranial hemorrhage was 25.4 years. All patients with a history of intracranial hemorrhage were classified as Rankin grade I or II at a mean follow-up interval of 6.0 years. A history of cerebral infarction or transient ischemic attack was found in 29.6% of patients with HHT and a pulmonary arteriovenous fistula. Conclusions-The risk of intracranial hemorrhage is low among people with HHT. Furthermore, a majority of these patients have a good functional outcome after hemorrhage. The data do not suggest a compelling indication for routine screening of patients with HHT for asymptomatic cerebral vascular malformations. 1 The estimated prevalence is 1 or 2 cases per 100 000. 1,2 Chromosomes 9q and 12q have been implicated in the inheritance of this disease. 3-7 A family history of HHT, although not required to make the diagnosis, is almost universally present. The vascular malformations of HHT may occur in multiple organs, including the lung, liver, kidney, and brain. 8,9 Epistaxis is the most common presentation, followed by gastrointestinal bleeding. 10,11 Pulmonary arteriovenous fistulae (AVFs) are often accompanied by dyspnea or hemoptysis and, less frequently, ischemic neurological symptoms. [12][13][14] Telangiectasias are frequently noted on the skin and mucous membranes, often not appearing until the second or third decade. 8,9 Brown et al 15,16 have reported that the detection rate of intracranial vascular malformations in a population-based study in the most recent time period was 2.75 per 100 000 person-years. The prevalence of intracranial hemorrhage from a vascular malformation was 7.50 per 100 000 people in the population at large. 15,16 Patients with HHT are thought to be at increased risk for harboring cerebral vascular malformations compared with the entire population. Arteriovenous malformations (AVMs), cavernous malformations, dural arteriovenous fistulae, and aneurysms have all been reported in these patients ( Figure 1). 14,17-24 Vascular malformations are found throughout the central nervous system, including the spinal cor...

show abstract

A third locus for hereditary haemorrhagic telangiectasia maps to chromosome 12q

Cited by 125 publications

References 0 publications

A hereditary haemorrhagic telangiectasia family with pulmonary involvement is unlinked to the known HHT genes, endoglin and ALK-1

A hereditary haemorrhagic telangiectasia family with pulmonary involvement is unlinked to the known HHT genes, endoglin and ALK-1

Mutant endoglin in hereditary hemorrhagic telangiectasia type 1 is transiently expressed intracellularly and is not a dominant negative.

Cerebrovascular Manifestations in 321 Cases of Hereditary Hemorrhagic Telangiectasia

Contact Info

Product

Resources

About