Usefulness of COL4A1 Gene Sequencing

PICHON RIVIERE, A.; AUGUSTOVSKI, F. A.; GARCIA MARTI, S.; GLUJOVSKY, D.; ALCARAZ, A.; LOPEZ, A.; BARDACH, A.; CIAPPONI, A; ROMANO, M

Documento de Evaluación de Tecnologías Sanitarias

IECS

Año: 2012 p. 1 - 30

1668-2793

Mutations in the COL4A1 gene which encodes collagen, type IV alpha-1, are associated with porencephaly, pediatric hemiparesis, lacunar stroke , micro-bleeding, incidental aneurisms and systemic findings in eyes and kidneys. They have been recently recognized as one of the monogenic causes of small vessel disease which may be present in adults. Technology At present, for COL4A1 gene mutation there are two genetic tests available (not in Argentina): The COL4A1 DNA genomic sequence test which detects small intragenic insertions and deletions, missense mutations. The second available test is the gene deletion/duplication test. Quantitative PCR and real-time PCR may be used. Purpose To assess the evidence available on the efficacy, safety and coverage related aspects regarding the usefulness of COL4A1 gene sequencing. Methods A systematic bibliographic search was carried out on the main databases: DARE, NHS EED, on Internet general search engines, in health technology evaluation agencies and health sponsors. Priority was given to the inclusion of systematic reviews; controlled, randomized clinical trials (RCTs); health technology assessments and economic evaluations; clinical practice guidelines and coverage policies of other health systems. Results No systematic reviews, clinical trials, clinical practice guidelines or coverage policies evaluating the usefulness of COL4A1 gene sequencing were found. A narrative review is included due to the scarce information available on the subject. The Narrative Review is a chapter of the book "Gene reviews", updated in March, 2011. The disease diagnosis is based on clinical manifestations and the genetic test. COL4A1 gene-related disorders are autosomal dominant inherited thus each child of a person with COL4A1 has 50% likelihood of inheriting the mutation. The rate of cases resulting from de novo mutations is unknown. For the assessment of parents whose child has the mutation, first, a medical record review, MRI, ophthalmologic examination and eventually genetic testing are recommended. Therefore, a negative family history cannot be confirmed until the adequate assessments are performed. Penetrance is close to 100%, age of onset and severity of symptoms vary within the family. This test is not carried out in Argentina. The sample shall be sent to Germany. The cost of the genomic sequencing test in the code region is 1,500.00 Euros and the screening of a family member screening is 150.00 Euros. Conclusions The spectrum of COL4A1 gen-related diseases has been recently described and there are still few cases reported worldwide, consequently, all the recommendations are based on expert opinions. Diagnosis is based on clinical manifestations (already described in the introduction) and genetic testing. The mutation genetic test may be useful in individuals with high clinical suspect disease. Despite the fact that there is no specific treatment for the disease, a support treatment and genetic counseling may be provided. This may also be useful in first degree family members of a confirmed case.