Determination Of Mutations In ALK-1 Gene In Chinese Family With Hereditary Hemorrhagic Telangiectasia Disease

Hereditary hemorrhagic telangiectasia (HHT) is an autosomaldominant vascular dysplasia leading to telangiectases andarteriovenous malformations of skin ,mucosa and viscera. Epistaxisand gastronintestin-Nal bleeding are frequent complications ofmucosal involvement.Visceral Involvement includes that of the lung,liver and brain. With the development of medical technology andknowledge , clinical doctors have realized that the importance of HHT.HHT occurs with wide and geographic distribution. But there were noepidemic statistics in china of HHT. Mutations in the ENG gene onchromosome 9(HHT1) and in the ALK-1 gene on chromosome12(HHT2) have been reported as causes of hereditary hemorrhagictelangiectasia (HHT). HHT-3 gene probably maps to thechromosome 5. At present, 129 different mutations concerning HHThave been reported .Among these, 79 are related to the mutation ofENG, and others are involved in mutations of ALK-1. Sequencing ofENG and ALK-1 coding regions is available on a clinical basis andwill detect missense and deletions and splice site mutations, nonsensemutations in genes. Actual study indicates haploinsufficency leads toHHT. Because the most common clinical manifestation is spontaneousand recurrent nose bleeding beginning at approximately 12 years ofage, patients often see ENT. The diagnosis of HHT is considereddefinite in an individual if three or more of the following four criteriaare present, suspected if two of the following four criteria are present,unlikely if fewer than two findings are present. ①Nosebleeds–spontaneous and recurrent. ②T elangiectases –multilple, atcharacteristic sites including lips ,oral cavity ,finger and nose .③ Internal telangiectases or AVM-lung, brain, GI, liver or spinal . ④Family history –parent, sibling, or child with HHT according to thesecriteria. There is evidence of genetic heterogeneity of HHT Accordingto the standard of HHT diagnosis ,we found a Chinese hereditaryhemorrhagic telangiectasia family at otolaryngology department.Thefamily includes 53 memebers. Sixteen cases of HHT were found in the53 persons .We perfomed a questionnaire-based study to clinicalfeatures of the family members .Purpose: To investigate the clinical features and gene mutations of aChinese hereditary hemorrhagic telangiectasia family .Patients and Methods : We investigated the 13 family members ofHHT patients on an outpatient basis . The thirteen family membersunderwent detailed clinical and experimental examinations .Proband ,female ,4 years old ,has spontaneous and recurrentnosebleeds for one year. She received nasal cavity endoscopy toobserve the capillaries in right nasal mucosa .A dot telangiectases isobserved on the left elbow .5-10ml peripheral blood sample weredrawn from each person of 13 family members and healthypeople .Genomic DNA was prepared from 1ml peripheral bloodlymphocytes of patients. The exon 3,4,7and 8 of the activinreceptor-like kinase 1(ALK-1) gene of the family people and healthypeople were amplified by polymerase chain reation (PCR).Thendenatured products of PCR were subject to single srand conformationpolymorphism (SSCP) analysis. Analysis of single strandedconformation polymorphism were performed on 6% homogenouspolyacrylam ide gel.Conclusion:The hereditary hemorrhagic telangiectasia of the familyis caused by a mutation of ALK-1 gene. The mutation is on exon 3 ofthe ALK-1 gene .