Introduction

The bestrophinopathies are a group of inherited retinal dystrophies due to mutations in BEST1 and characterised by reduced vision and an early and significant reduction in the electro-oculogram (EOG) light rise. Diseases attributable to BEST1 mutations include Best disease or vitelliform macular dystrophy (VMD) and autosomal recessive bestrophinopathy (ARB).

Referral information

Mutation screening of the BEST1 gene is available for affected individuals. Pre-symptomatic, carrier testing and prenatal diagnosis are available in families with a previously identified mutation. Confirmation of mutations identified in research laboratories.

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Introduction

Choroideremia is an X-linked ocular disorder that leads to the degeneration of the choriocapillaris, retinal pigment epithelium, and the retinal photoreceptor of the eye due to mutations in the CHM gene, which encodes Rab escort protein-1 (REP1).

Referral information

Mutation screening of the CHM gene is available for male patients with a suspected diagnosis of choroideremia. Mutation scanning of obligate carrier females may also be considered. Please contact the laboratory before referring females for mutation scanning. Pre-symptomatic, carrier testing and prenatal diagnosis are available in families with a previously identified mutation. Confirmation of mutations identified in research laboratories.

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Introduction

Doyne Honeycomb Retinal Dystrophy is an autosomal dominant disorder characterised by small round white spots (drusen) involving the posterior pole of the eye, including the areas of the macula and optic disc, appear in early adult life followed by progressive retinal degeneration. Alternative types of referral and variations of disease/symptoms include: Doyne Honeycomb Degeneration of Retina; Malattia Leventinese and Autosomal Dominant Radial Drusen. Screening is limited to the p.(Arg345Trp) mutation in the EGF-Containing Fibulin-like Extracellular Matrix Protein 1 (EFEMP1) gene. This mutation is the only mutation associated with DHRD.

Referral information

Mutation screening is available for affected individuals with a clinical diagnosis of DHRD/dominant Drusen. Pre-symptomatic testing is available in families with a previously identified mutation.

View full test details for Doyne Honeycomb Retinal Dystrophy (DHRD) mutation analysis

Introduction

Late-onset retinal degeneration (LORD) is an autosomal dominant disorder characterized by onset in the fifth to sixth decade with night blindness and punctate yellow-white deposits in the retinal fundus, progressing to severe central and peripheral degeneration, with choroidal neovascularization and chorioretinal atrophy. We offer testing for the c.489C>G p.(Ser163Arg) and c.489C>A p.(Ser163Arg) mutations in CTRP5/C1QTNF5. The p.(Ser163Arg) substitution is the only mutation associated with LORD.

Referral information

Mutation screening is available for affected individuals with LORD. Pre-symptomatic testing is available in families with a previously identified mutation.

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Introduction

Macular Dystrophy is characterised by a loss of central vision due to the degeneration of the central retinal area or Macular. Between 7 and 20% of Macular Dystrophy is caused by mutations in the PRPH2 (RDS/Peripherin) gene.

Referral information

Mutation screening is available for affected individuals with macular dystrophy. Pre-symptomatic and carrier testing are available in families with a previously identified mutation. Confirmation of mutations identified in research laboratories.

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Introduction

We offer a comprehensive next generation sequencing mutation scan of 205 genes known to cause a variety of ophthalmic disorders. These are divided into 11 subpanels depending on the clinical indication (see below). We provide a comprehensive scientific interpretation of variants found and issue a report summarising our findings.

Referral information

We offer mutation scanning in affected individuals. This testing is relevant for sporadic cases or patients with a family history consistent with an autosomal dominant, recessive or X-linked family history of an ophthalmic disorder. On identification of a pathogenic change in an index case, presymptomatic and carrier testing of relatives of an index case can be offered. Testing of family members is often required to help interpret the findings. Referrals should be accompanied by a clinical diagnosis and details of family history. Referrals also should be accompanied by a completed standard referral request form and a clinical proforma indicating which panel(s) is required. For optimal results please send a fresh EDTA blood sample (1-4mls) or a minimum of 3 microgrammes of extracted DNA.

View full test details for Ophthalmic Disorders

Introduction

We offer a comprehensive next generation sequencing mutation scan of 176 genes known to cause inherited retinal disease including an interpretation of variants found.

Referral information

We offer mutation scanning in affected individuals and obligate carriers. This testing is relevant for sporadic cases or patients with a family history consistent with an autosomal dominant, recessive or X-linked family history of retinal degeneration. Given the nature of the genes analysed this test is also appropriate for patients with macular dystrophy, achromatopsia, congenital stationary night blindness as well as Usher, Bardet-Biedl, Joubert, Senior-Loken and Cohen syndromes. Testing of family members may be required to help interpret our findings. On identification of a pathogenic change in an index case presymptomatic and carrier testing of relevant relatives of the proband can be offered. Referrals should be accompanied by a clinical diagnosis and details of family history. Referrals should also be accompanied by a completed standard referral request form and a completed NGS clinical proforma. Note that this test does not include RPGR ORF15; if this test is required please indicate on the referral. At present, NGS technology will not reliably detect large deletions and duplications. The current test service for the X-linked form of RD remains available (see our Ophthalmic Genetics page).

View full test details for Retinal Degeneration Conditions

Introduction

Retinoblastoma (Rb) is a malignant intraocular tumour occurring predominantly in children under 5 years. The incidence of this disease is 1 in 15,000-25,000. Approximately 35 to 45% of all Rb cases are heritable as defined by a family history and/or the presence of bilateral or multifocal tumours. In familial cases, the disease is autosomal dominant with high penetrance (90%). The remainder usually present as unilateral solitary tumours, with approximately 15% of these unilateral cases having a germline mutation. The gene for retinoblastoma (RB1) is localised at 13q14.

Referral information

Mutation screening in the blood of index cases with a family history or bilateral Rb. Mutation screening in tumours from cases of sporadic unilateral Rb. Pre-symptomatic testing of relatives of an index case with a previously identified RB1 mutation. Prenatal diagnosis where a germline mutation has been identified in a parent.. Linkage analysis for families at risk in whom no mutations have been identified.

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Introduction

Sorsby fundus dystrophy (SFD) is an autosomal dominant macula dystrophy with middle age onset. Patients lose central vision as a result of extra-cellular deposits and thickening in Bruch’s membrane, sub-retinal neovascularization, and atrophy of the ocular tissues. The SFD phenotype shares extensive clinical similarity with age-related macular degeneration (AMD), in particular the more severe or “wet” form of AMD. Mutations in the gene encoding tissue inhibitor of metalloproteinases-3 (TIMP-3) have been shown to be responsible for SFD. These mutations are confined to exon 5 of TIMP-3 and its intron4/exon5 acceptor splice site

Referral information

Mutation screening is available for affected individuals with suspected SFD. Pre-symptomatic testing is available for families with a previously identified mutation.

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Introduction

XLRP (X-linked retinitis pigmentosa) accounts for 8-17% of familial RP cases.  XLRP is the least frequent and the most severe form of RP.  It is associated with an early age of onset (although this can range from 4-55 years) and a rapid progression, often leading to severe visual handicap before the fourth decade.  XLRP is genetically heterogeneous and so far two disease genes have been identified, retinitis pigmentosa GTPase regulator gene (RPGR) and retinitis pigmentosa 2 (RP2).  Mutations in RPGR account for ~75% of XLRP patients and a 1.7kb alternatively spliced exon, exon ORF15, harbours between 30-66% of RPGR pathogenic changes.  RP2 mutations have also been identified throughout the RP2 gene in patients with XLRP.

Referral information

For male patients with sporadic RP and no family history, mutation screening is undertaken for RPGR exon ORF15 only. For male patients with a family history of RP or cone/rod dystrophy and a possible X-linked inheritance, initial mutation screening is undertaken for RPGR exon ORF15, and if there remains a strong clinical suspicion of XLRP we can extend screening to the remainder of RPGR and RP2 following a request from the referring clinician. Mutation scanning of obligate carrier females may be considered. Please contact the laboratory before referring females for mutation scanning.  Pre-symptomatic, carrier testing and prenatal diagnosis (where appropriate) are available in families with a previously identified mutation. Confirmation of mutations identified in research laboratories.

View full test details for X-Linked Retinitis Pigmentosa