SCIENTIFIC BACKGROUND

ABCA4, C8orf37, CA4, CDHR1, CERKL, CRB1, DHDDS, EYS, FAM161A, FSCN2, IDH3B, IFT172, IMPDH1, IMPG2, KIZ, KLHL7, MAK, MERTK, NEK2, NR2E3, NRL, OFD1, PCARE, PDE6A, PDE6B, PDE6G, PRCD, PROM1, PRPF3, PRPF4, PRPF6, PRPF8, RBP3, RHO, ROM1, RP1, RP9, RPE65, RPGR, SAG, SEMA4A, SLC7A14, SNRNP200, TOPORS, TULP1, USH2A, ZNF408, ZNF513

Category:

Scientific Background

Familial retinopathies occur in several diseases with overlapping symptoms, such as retinitis pigmentosa (RP), Leber congenital amaurosis (LCA), Stargardt disease, Usher syndrome (USH), Bardet-Biedl syndrome (BBS) and Senior-Løken syndrome.

 

The incidence of RP is 1:3,000-5,000, with syndromic diseases being rarer. In most cases only the retina is clinically affected. Symptoms are characterized by night blindness and a slow, progressive loss of central vision from about the age of 20 that is initially limited to degeneration of the rod photoreceptors on the retina. The cones may also be affected later. However, there are also syndromic diseases in which retinal dystrophy is the first symptom and which are difficult to differentiate in the early stages.

 

Patients with USH have hearing loss in addition to RP. Even in the case of pure retinopathies, differential diagnosis can be difficult, because the symptoms often overlap and the full spectrum of the disease can only become apparent after decades due to the usually progressive course of disease. In addition, intrafamilial variability is known. The causes of RP are very heterogeneous, as more than 80 causative genes are known. 35-60% of RP cases have autosomal recessive inheritance, 15-25% autosomal dominant inheritance and 15% X-linked inheritance. Pathogenic variants in the USH2A gene cause 10-15% of the syndromic form of RP—autosomal recessive inherited USH. In recessively inherited cases, pathogenic changes in the genes RPGR including ORF15 and RP2 can be detected in up to 85% of cases. Approximately 25% of all non-syndromic RP cases are due to pathogenic variants in the rhodopsin gene (RHO) that have autosomal dominant inheritance. Using NGS, the genes for the different forms of RP can be analyzed in parallel (gene panel diagnostics). Diagnostic sensitivity is 20-30% for autosomal recessive forms, 80-85% for dominant forms and over 85% for syndromic forms.

 

References

Talib et al. 2018, Invest Ophthalmol Vis Sci 59:4123 / Almoguera et al. 2015, PLoS One 10:e0133624 / Chiang et al. 2015, Expert Rev Mol Diagn 15:1269 / Daiger et al. 2013, Clin Genet 84:132

GENES

ABCA4, C8orf37, CA4, CDHR1, CERKL, CRB1, DHDDS, EYS, FAM161A, FSCN2, IDH3B, IFT172, IMPDH1, IMPG2, KIZ, KLHL7, MAK, MERTK, NEK2, NR2E3, NRL, OFD1, PCARE, PDE6A, PDE6B, PDE6G, PRCD, PROM1, PRPF3, PRPF4, PRPF6, PRPF8, RBP3, RHO, ROM1, RP1, RP9, RPE65, RPGR, SAG, SEMA4A, SLC7A14, SNRNP200, TOPORS, TULP1, USH2A, ZNF408, ZNF513

ASSOCIATED TESTS

How to order

LATEST ARTICLES

Cystic fibrosis (CF) is a life-threatening, progressive, inherited condition that causes severe damage to the body, primarily affecting the organs of...

Read more

Down syndrome is a genetic condition caused by the presence of an extra copy of chromosome 21. It affects physical growth, facial features, and cogni...

Read more

Every year on April 25th, DNA Day celebrates the discovery of DNA’s double helix and the advances we’ve made in understanding genetics. D...

Read more

Neurodevelopmental disorders (NDDs) have diverse genetic origins, making diagnosis challenging. A new study analyzing over 1,100 pediatric patients f...

Read more

Colorectal cancer (CRC) remains one of the most prevalent and deadly cancers worldwide, with a significant number of cases presenting at an advanced ...

Read more

Carrier screening is a genetic test designed to identify whether an individual carries a gene with changes (mutations) associated with inherited diso...

Read more

Trisomy 13, also known as Patau syndrome, is a genetic condition in which cells in the body have three copies of chromosome 13 instead of two. The co...

Read more

The human brain develops through a complex series of events, with genes carefully regulating the formation of neurons and glial cells. A recent study...

Read more

Rare diseases affect between 300 and 400 million people worldwide – more than cancer and AIDS combined [1, 2], but despite this, many people face a...

Read more

Rosalind Elsie Franklin was a brilliant and meticulous research scientist whose interdisciplinary work made fundamental contributions to various area...

Read more