A Novel Splicing Mutation in the ACVRL1/ALK1 Gene as a Cause of HHT2

Díaz, Suriel Errasti; Peñalva, Mercedes; Recio-Poveda, Lucía; Vilches, Susana; Casado‐Vela, Juan; Pérez-Pérez, Julián; Botella, Luisa María; Albiñana, Virginia; Cuesta, Ángel M.

doi:10.3390/jcm11113053

Cited by 3 publications

(3 citation statements)

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“…The abnormal signal transduction of the bone morphogenetic protein leads to developmental vascular anomalies, such as arteriovenous fistula and disorders of vascular constriction that lead to vasodilation[ 22 ]. ACVRL1 mutations cause autosomal vascular dysplasia, which is commonly referred to as hereditary hemorrhagic telangiectasia type 2 (HHT2)[ 25 , 26 ]. HHT2 is acquired via autosomal dominant inheritance, and its homozygous mutation is fatal.…”

Section: Discussionmentioning

confidence: 99%

Link between mutations in ACVRL1 and PLA2G4A genes and chronic intestinal ulcers: A case report and review of literature

Tang,

Zhang,

Wang

et al. 2024

World J Gastrointest Surg

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BACKGROUND Genetic factors of chronic intestinal ulcers are increasingly garnering attention. We present a case of chronic intestinal ulcers and bleeding associated with mutations of the activin A receptor type II-like 1 (ACVRL1 ) and phospholipase A2 group IVA (PLA2G4A ) genes and review the available relevant literature. CASE SUMMARY A 20-year-old man was admitted to our center with a 6-year history of recurrent abdominal pain, diarrhea, and dark stools. At the onset 6 years ago, the patient had received treatment at a local hospital for abdominal pain persisting for 7 d, under the diagnosis of diffuse peritonitis, acute gangrenous appendicitis with perforation, adhesive intestinal obstruction, and pelvic abscess. The surgical treatment included exploratory laparotomy, appendectomy, intestinal adhesiolysis, and pelvic abscess removal. The patient’s condition improved and he was discharged. However, the recurrent episodes of abdominal pain and passage of black stools started again one year after discharge. On the basis of these features and results of subsequent colonoscopy, the clinical diagnosis was established as inflammatory bowel disease (IBD). Accordingly, aminosalicylic acid, immunotherapy, and related symptomatic treatment were administered, but the symptoms of the patient did not improve significantly. Further investigations revealed mutations in the ACVRL1 and PLA2G4A genes. ACVRL1 and PLA2G4A are involved in angiogenesis and coagulation, respectively. This suggests that the chronic intestinal ulcers and bleeding in this case may be linked to mutations in the ACVRL1 and PLA2G4A genes. Oral Kangfuxin liquid was administered to promote healing of the intestinal mucosa and effectively manage clinical symptoms. CONCLUSION Mutations in the ACVRL1 and PLA2G4A genes may be one of the causes of chronic intestinal ulcers and bleeding in IBD. Orally administered Kangfuxin liquid may have therapeutic potential.

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Section: Discussionmentioning

confidence: 99%

Link between mutations in ACVRL1 and PLA2G4A genes and chronic intestinal ulcers: A case report and review of literature

Tang,

Zhang,

Wang

et al. 2024

World J Gastrointest Surg

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“…LOF mutations of the ENG gene (located on chromosome 9q34.11) (OMIM 18301) [ 6 ], which encodes endoglin, are present in HHT1 [ 6 , 50 ], and mutations of the ACRVL1/ALK1 gene (OMIM 601284) (located on chromosome 12q13.13) [ 6 ] which encodes ALK1 (Activin A receptor, type II-like kinase 1 also called activin receptor-like kinase-1) are associated with HHT2 [ 51 , 52 ]. Other loci identified in patients with HHT are located on chromosome 5q31.3-32 (HHT3) [ 53 ] and chromosome 7p14 (HHT4) [ 54 ].…”

Section: Vascular Anomalies: Pi3k/akt/mtor Signaling Pathways (Pikopa...mentioning

confidence: 99%

The Genetic Architecture of Vascular Anomalies: Current Data and Future Therapeutic Perspectives Correlated with Molecular Mechanisms

Butnariu

Gorduza

Florea

et al. 2022

IJMS

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Vascular anomalies (VAs) are morphogenesis defects of the vascular system (arteries, capillaries, veins, lymphatic vessels) singularly or in complex combinations, sometimes with a severe impact on the quality of life. The progress made in recent years with the identification of the key molecular pathways (PI3K/AKT/mTOR and RAS/BRAF/MAPK/ERK) and the gene mutations that lead to the appearance of VAs has allowed the deciphering of their complex genetic architecture. Understanding these mechanisms is critical both for the correct definition of the phenotype and classification of VAs, as well as for the initiation of an optimal therapy and the development of new targeted therapies. The purpose of this review is to present in synthesis the current data related to the genetic factors involved in the etiology of VAs, as well as the possible directions for future research. We analyzed the data from the literature related to VAs, using databases (Google Scholar, PubMed, MEDLINE, OMIM, MedGen, Orphanet) and ClinicalTrials.gov. The obtained results revealed that the phenotypic variability of VAs is correlated with genetic heterogeneity. The identification of new genetic factors and the molecular mechanisms in which they intervene, will allow the development of modern therapies that act targeted as a personalized therapy. We emphasize the importance of the geneticist in the diagnosis and treatment of VAs, as part of a multidisciplinary team involved in the management of VAs.

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“…In this sense, the international collaboration reported by Errasti Díaz et al highlights the difficulties of performing a rather easy genetic test for a new mutation HHT in Peru [ 6 ]. In addition to the novelty of this new mutation, it should also shed light on and inspire international collaboration, due to the fact that the number of inhabitants can lead to thousands of HHT patients (and patients with many other rare diseases) remaining unidentified.…”

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confidence: 99%