X-Linked Retinitis Pigmentosa

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.

Technical information

Mutation scanning by bi-directional Sanger sequencing of RPGR exon ORF15. Mutation scanning of RPGR exons 1-14 and RP2 is undertaken using Next generation sequencing technology with all bases covered to 50x read depth, and confirmed using bi-directional Sanger sequencing. MLPA analysis is undertaken for any male patients where RPGR exon 1-14/RP2 PCR fragments fail to amplify. A proportion of missense changes cannot be classified in which case we may request further family studies.

Price & reporting times

Test Price NHS (£) Price non-NHS (£) TRT (calendar days)
RPGR exon ORF15 mutation scanning POA POA 56
RPGR exons 1-14 and RP2 POA POA 56
Single mutation test POA POA 28
Urgent/Predictive single mutation test POA POA 14
Prenatal diagnosis POA POA 3

Test validation & quality assurance - information for users

In our series a pathogenic variant is found in 55% of males with a family history of RP and in 7% of simplex cases. The laboratory is UKAS assessed against ISO 15189 standards.

Sample requirements

Pre-natal: amniotic fluid (minimum 15ml)/chorionic villus biopsy (CVB) (minimum 10mg) sample plus 4ml EDTA maternal blood sample

Post-natal: 4ml EDTA blood sample

Referral guidelines

Please see our referral guidelines for more information.

OMIM Number(s) - 31260 (RPGR) + 300757 (RP2)

Gene(s) - RPGR (including ORF15) and RP2

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