Clinical utility gene card for: Choroideremia

Moosajee, Mariya; Ramsden, Simon; Black, Graeme C M; Seabra, Miguel C.; Webster, Andrew R.

doi:10.1038/ejhg.2013.183

Cited by 40 publications

(52 citation statements)

References 18 publications

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“…Males from family 2 bearing the c.‐98C>T mutation manifested with chorioretinal disease, but with varying degrees of severity; proband 111 remained symptomatically mild, whereas in his maternal uncles 151 and 161, disease progression was more typical. CHM is known to exhibit a wide interfamilial, and also intrafamilial variability (Moosajee, Ramsden, Black, Seabra, & Webster, ). As the mutations c.‐98C>A and c.‐98C>T appear to completely abolish transcription, producing no detectable levels of CHM mRNA and REP‐1 protein in patient cells, it is not surprising for the disease to present in a classical manner consistent with phenotypes observed for the loss‐of‐function mutations.…”

Section: Discussionmentioning

confidence: 99%

Single-base substitutions in theCHMpromoter as a cause of choroideremia

et al. 2017

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45Although over 150 unique mutations affecting the coding sequence of CHM have been identified 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 peripheral vision (Karna, 1986;Roberts et al., 2002). 76To date, CHM has only been linked to mutations within the CHM gene, coding for REP-1 77 (Cremers et al., 1990). The protein serves as a molecular chaperone for small GTPases from the Rab proteins is essential for intracellular vesicular transport (Seabra et al., 1992; Seabra et al., 81 1993). A homologue, REP-2, encoded by CHML or choroideremia-like, functions similarly and 82 appears to compensate for the absence of REP-1 in all tissues except the eye (Cremers et al., 83 1994). CHM spans over 150 kb of Xq21.2 and contains 15 exons (van Bokhoven et al., 1994). A 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 Missense mutations predicted to alter protein structure or impair function (Sergeev et al., 2009; 91 Esposito et al., 2011), transposon insertions (Van Den Hurk et al., 2003), partial gene 92 duplications (Chi et al., 2013;Simunovic et al., 2016) and other variations are infrequently 93 found, but taken collectively, almost all known pathogenic variants in the CHM gene have been 94 loss of function mutations that abolish functional REP-1 (McTaggart et al., 2002; Simunovic et 95 al., 2016). Notably there is no apparent correlation between genotype and phenotype, with the 96 age at onset of symptoms, visual acuity and visual fields being unrelated to mutation type 97 (Freund et al., 2016;Simunovic et al., 2016). 98The promoter driving expression of CHM has been heretofore unidentified. Analyses of 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 Materials and Methods 128 Clinical Examination and Study Subjects 129This study was approved by the institutions' respective ethics review boards. All procedures 130 adhered to the tenets of the Declaration of Helsinki. Before participation, the purpose and risks 131 of the study were explained, and informed consent was obtained. Blood samples were drawn, 132 and a detailed pedigree and history was recorded. 133We studied 4 males affected by CHM and 1 carrier female from two unrelated families. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 (Anderson and Gusella, 1984). Cells were 157 maintained in RPMI-1640 supplemented with 15% fetal ...

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Section: Discussionmentioning

confidence: 99%

Single-base substitutions in theCHMpromoter as a cause of choroideremia

et al. 2017

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“…The guidelines for clinical use of the test are described in "Genetics home reference" (ghr.nlm.nih.gov), "Gene reviews" (8) and "Clinical Utility Gene Card" (10).…”

Section: Test Characteristics Experts Centers/published Guidelinesmentioning

confidence: 99%

Genetic testing for choroideremia

Abeshi

Zulian²,

Beccari

et al. 2017

The EuroBiotech Journal

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We studied the scientific literature and disease guidelines in order to summarize the clinical utility of the genetic test for choroideremia (CHM). CHM is an inherited X-linked recessive disorder associated with variations in the CHM gene. The overall prevalence of CHM varies from 1 in 50 000 to 1 in 100 000. Clinical diagnosis is based on clinical findings, ophthalmological examination, visual field, fundus autofluorescence, optical coherence tomography and electroretinography. The genetic test is useful for confirming diagnosis and for differential diagnosis, couple risk assessment and access to clinical trials.

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“…Resources for vitreoretinal specialists to learn more about genetic testing, genetic counseling, and molecular diagnostic techniques [25][26][27] and the laboratories conducting them are provided (Table 2). Available for choroideremia, 30 Usher syndrome, 31 achromatopsia, 32 and BEST1-related dystrophies. 33 • With emerging technologies in molecular diagnostics, gene delivery and editing tools, and diverse vision rescue strategies, the potential of gene therapy for treatment of IRDs continues to climb.…”

Section: Diseasesmentioning

confidence: 99%