Characteristic of the test: (includes 3 genes)

CRX (OMIM #602225)

IMPDH1 (OMIM #146690)

OTX2 (OMIM #600037)

Basic characteristics of the clinical phenotype
Leber congenital amaurosis (LCA, OMIM #204000) is the most severe form of inherited retinal degeneration that is usually present at birth or manifests in the first months of a child's life. LCA is clinically characterized by reduced visual function, often accompanied by nystagmus, photophobia, farsightedness (hyperopia), significantly reduced electroretinogram, and keratoconus. The estimated incidence of LCA is 2-3/100,000 births and accounts for 10-18% of cases of congenital blindness. A milder form of hereditary retinal degeneration is generally considered juvenile retinal pigment degeneration (Retinitis pigmentosa, RP), which is a group of hereditary retinal dystrophies with a frequency of 1:4,000 worldwide. LCA and juvenile RP overlap clinically and genetically, with an intermediate phenotype corresponding to the clinic of Cone-rod retinal degeneration (CORD) or early-onset retinal degeneration. Cone-rod retinal degeneration is 10 times rarer than RP - 1:40,000.

Leber congenital amaurosis is a genetically heterogeneous disease and is most often inherited in an autosomal recessive pattern. However, an autosomal dominant form is also known, and 3 genes, mutations in which lead to LCA, have been identified so far - CRX, IMPDH1, OTX2.

Reasons for referring:
Candidates for this test are all patients with symptoms of LCA or CORD, as well as relatives of the patients in whom the mutation is known.

Interpretation of results:
· Detection of point mutations and small deletions/insertions in the CRX, IMPDH1, OTX2 genes will allow a genetic diagnosis of LCA or CORD.

· Presence of large deletions and insertions cannot be detected by this method. A combination with a suitable CNV analysis (MLPA, aCGH) is recommended for their detection.
· The genetic counselor will interpret and answer all questions about your result.

Method: Sanger sequencing.
The method involves bi-directional DNA sequencing of all coding exons and intron-exon boundaries of the CRX, IMPDH1 and OTX2 genes. The laboratory offers single exon sequencing in relatives of the patients to determine the carrier status in cases where the mutation is known (Test #182).

Sensitivity of the method: 99.5%

What does the test involve?
· DNA isolation and sample storage.
· Direct sequencing of target genes/gene regions to detect pathogenic mutations.
· Forming a written result of the genetic test.
· Diagnostic interpretation of results and genetic counseling.

Biological material: Venous blood or DNA
For more information, please read the "Biological material requirements and shipping information" carefully.