Hereditary Hemorrhagic Telangiectasia: ACVRL1, ENG

Alternate test name

HHT; Osler-Weber-Rendu Disease

Gene name / Alternate gene name

Gene name(s):

ACVRL1
ENG

Alt Gene Name(s): ALK1, HHT1, HHT2

Protein

Activin A receptor type II-like 1, Endoglin

Lab area

Genome Diagnostics - Molecular Genetics

Method and equipment

Deletion/duplication analysis via MLPA; Sequencing

Expected turn-around time

Pregnant/STAT: 2-3 weeks Routine: 4-6 weeks

Specimen type

Blood; extracted DNA is not accepted for ENG and ACVRL1 Deletion/Duplication Analysis.

If sending a prenatal sample, please contact the laboratory prior to sending sample to discuss sample requirements.

For details about specimen requirements, please refer to: Specimen Type & Requirements (PDF).

Specimen requirements

Blood: 5-10 mL in EDTA, 0.5 mL in EDTA (neonate);
DNA-minimum 10 ug in 100 uL low TE (pH8.0)

Storage and transportation

Room Temperature

For details about specimen requirements, please refer to: Specimen Type and Requirements

DNA extracted at an external lab is not accepted for MLPA testing.

Special requirements

Special Instructions for Genome Diagnostics Samples

If sample shipment >48 hours, ship on ice.

Shipping information

The Hospital for Sick Children

Division of Genome Diagnostics

555 University Avenue, Black Wing, Room 3416

Toronto, ON

Canada

M5G 1X8

Phone: 416-813-7200 ext. 2

Hours: Monday to Friday, 8 a.m. to 4:30 p.m.

Off hours: Please send to Rapid Response Laboratory, 555 University Avenue, Room 3642

Email Molecular Lab: molecular.lab@sickkids.ca

Email Cytogenetics: cytogenetics.requests@sickkids.ca

Requisition

Hereditary Hemorrhagic Telangiectasia: ACVRL1, ENG - requisition

Background and clinical significance

Hereditary hemorrhagic telangiectasia (HHT) results from the presence of multiple arteriovenous malformations (AVMs) in which intervening capillaries between arteries and veins are absent, resulting in direct connections between arteries and veins. Small AVMs or telangiectases near the skin surface and surface of oral and gastrointestinal (GI) mucosa membranes often rupture and bleed with minor trauma. Large AVMs often cause more severe symptoms when they occur in brain, lung, GI tract or more rarely liver and spine. Complications from bleeding or shunting may be sudden and catastrophic.

HHT is an autosomal dominant disorder which can be divided into two clinically indistinct forms based on the protein defect: HHT1 is caused by defects in the endoglin protein encoded by the ENG gene located on chromosome 9 at 9q34.1 while HHT2 is caused by defects in the serine/threonine receptor kinase R3 encoded by the ACVRL1 (ALK1) gene located on chromosome 12 at 12q11-q14. Approximately 80-90% of all mutations causing HHT1 or HHT2 are point mutations or small insertions/deletions. Deletions in the ENG gene may also cause up to 10% of HHT.

HHT is present when an individual has one copy of the defective gene (ENG or ACVRL1). Silent carriers may not be affected themselves by HHT, however, they may transmit the defective gene to their offspring. There is a 50% chance that their baby will have the gene for HHT and thus may develop symptoms at some stage in their life. There is a 50% chance that the baby will not have HHT.

See related information sheet: Hereditary Hemorrhagic Telangiectasia

Disease condition

Hereditary Hemorrhagic Telangiectasia