Long-term follow-up of patients with retinitis pigmentosa type 12 caused by CRB1 mutations: A severe phenotype with considerable interindividual variability

Inge B. Mathijssen, Ralph J. Florijn, L. Ingeborgh Van Den Born, Renate C. Zekveld-Vroon, Jacoline B. Ten Brink, Astrid S. Plomp, Frank Baas, Hanne Meijers-Heijboer, Arthur A.B. Bergen, Mary J. Van Schooneveld

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Purpose: To examine the long-term clinical course and variability in a large pedigree segregating CRB1 type autosomal recessive retinitis pigmentosa. Methods: An observational case study of 30 patients with CRB1 type autosomal recessive retinitis pigmentosa, homozygous for the CRB1 c.3122T > C; p.(Met1041Thr) mutation from a Dutch genetically isolated population in which the CRB1 gene was originally identified. The authors evaluated medical records, analyzed a questionnaire, and performed a comprehensive ophthalmic examination, including optical coherence tomography. Results: Mean follow-up was 19 years (range 0-45 years, SD 15 years). With aging, patients showed progressive visual decline, deterioration of visual fields, increasing narrowing of the anterior chamber, increased prevalence of cataract, and an increase in the amount of intraretinal pigmentations. Fifty percent of patients had a visual acuity of ≤0.3 at Age 18 and of ≤0.1 at Age 35. Electroretinogram responses were severely reduced or absent already at a young age and optical coherence tomography showed increased retinal thickness with often cystoid maculopathy at young age, and thinning of the retina and disorientation of the photoreceptor layer in the late stages. The clinical course showed considerable interindividual variability, but intraindividual similarity between both eyes was the rule. Conclusion: The wide and variable clinical spectrum in patients with the same CRB1 mutation supports the hypothesis that the CRB1 type autosomal recessive retinitis pigmentosa-phenotype is modulated by other factors. The clinical variability will make it harder to evaluate the effect of (upcoming) therapies for retinitis pigmentosa, although because of the intraindividual similarity between both eyes, the contralateral eye can be used as an excellent internal control.

Original languageEnglish
Pages (from-to)161-172
Number of pages12
JournalRetina
Volume37
Issue number1
DOIs
Publication statusPublished - 2017

Cite this

Mathijssen, I. B., Florijn, R. J., Van Den Born, L. I., Zekveld-Vroon, R. C., Ten Brink, J. B., Plomp, A. S., ... Van Schooneveld, M. J. (2017). Long-term follow-up of patients with retinitis pigmentosa type 12 caused by CRB1 mutations: A severe phenotype with considerable interindividual variability. Retina, 37(1), 161-172. https://doi.org/10.1097/IAE.0000000000001127
Mathijssen, Inge B. ; Florijn, Ralph J. ; Van Den Born, L. Ingeborgh ; Zekveld-Vroon, Renate C. ; Ten Brink, Jacoline B. ; Plomp, Astrid S. ; Baas, Frank ; Meijers-Heijboer, Hanne ; Bergen, Arthur A.B. ; Van Schooneveld, Mary J. / Long-term follow-up of patients with retinitis pigmentosa type 12 caused by CRB1 mutations : A severe phenotype with considerable interindividual variability. In: Retina. 2017 ; Vol. 37, No. 1. pp. 161-172.
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title = "Long-term follow-up of patients with retinitis pigmentosa type 12 caused by CRB1 mutations: A severe phenotype with considerable interindividual variability",
abstract = "Purpose: To examine the long-term clinical course and variability in a large pedigree segregating CRB1 type autosomal recessive retinitis pigmentosa. Methods: An observational case study of 30 patients with CRB1 type autosomal recessive retinitis pigmentosa, homozygous for the CRB1 c.3122T > C; p.(Met1041Thr) mutation from a Dutch genetically isolated population in which the CRB1 gene was originally identified. The authors evaluated medical records, analyzed a questionnaire, and performed a comprehensive ophthalmic examination, including optical coherence tomography. Results: Mean follow-up was 19 years (range 0-45 years, SD 15 years). With aging, patients showed progressive visual decline, deterioration of visual fields, increasing narrowing of the anterior chamber, increased prevalence of cataract, and an increase in the amount of intraretinal pigmentations. Fifty percent of patients had a visual acuity of ≤0.3 at Age 18 and of ≤0.1 at Age 35. Electroretinogram responses were severely reduced or absent already at a young age and optical coherence tomography showed increased retinal thickness with often cystoid maculopathy at young age, and thinning of the retina and disorientation of the photoreceptor layer in the late stages. The clinical course showed considerable interindividual variability, but intraindividual similarity between both eyes was the rule. Conclusion: The wide and variable clinical spectrum in patients with the same CRB1 mutation supports the hypothesis that the CRB1 type autosomal recessive retinitis pigmentosa-phenotype is modulated by other factors. The clinical variability will make it harder to evaluate the effect of (upcoming) therapies for retinitis pigmentosa, although because of the intraindividual similarity between both eyes, the contralateral eye can be used as an excellent internal control.",
keywords = "Clinical course, CRB1, Phenotype, Retinitis pigmentosa, RP12, Variability",
author = "Mathijssen, {Inge B.} and Florijn, {Ralph J.} and {Van Den Born}, {L. Ingeborgh} and Zekveld-Vroon, {Renate C.} and {Ten Brink}, {Jacoline B.} and Plomp, {Astrid S.} and Frank Baas and Hanne Meijers-Heijboer and Bergen, {Arthur A.B.} and {Van Schooneveld}, {Mary J.}",
year = "2017",
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language = "English",
volume = "37",
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Mathijssen, IB, Florijn, RJ, Van Den Born, LI, Zekveld-Vroon, RC, Ten Brink, JB, Plomp, AS, Baas, F, Meijers-Heijboer, H, Bergen, AAB & Van Schooneveld, MJ 2017, 'Long-term follow-up of patients with retinitis pigmentosa type 12 caused by CRB1 mutations: A severe phenotype with considerable interindividual variability' Retina, vol. 37, no. 1, pp. 161-172. https://doi.org/10.1097/IAE.0000000000001127

Long-term follow-up of patients with retinitis pigmentosa type 12 caused by CRB1 mutations : A severe phenotype with considerable interindividual variability. / Mathijssen, Inge B.; Florijn, Ralph J.; Van Den Born, L. Ingeborgh; Zekveld-Vroon, Renate C.; Ten Brink, Jacoline B.; Plomp, Astrid S.; Baas, Frank; Meijers-Heijboer, Hanne; Bergen, Arthur A.B.; Van Schooneveld, Mary J.

In: Retina, Vol. 37, No. 1, 2017, p. 161-172.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Long-term follow-up of patients with retinitis pigmentosa type 12 caused by CRB1 mutations

T2 - A severe phenotype with considerable interindividual variability

AU - Mathijssen, Inge B.

AU - Florijn, Ralph J.

AU - Van Den Born, L. Ingeborgh

AU - Zekveld-Vroon, Renate C.

AU - Ten Brink, Jacoline B.

AU - Plomp, Astrid S.

AU - Baas, Frank

AU - Meijers-Heijboer, Hanne

AU - Bergen, Arthur A.B.

AU - Van Schooneveld, Mary J.

PY - 2017

Y1 - 2017

N2 - Purpose: To examine the long-term clinical course and variability in a large pedigree segregating CRB1 type autosomal recessive retinitis pigmentosa. Methods: An observational case study of 30 patients with CRB1 type autosomal recessive retinitis pigmentosa, homozygous for the CRB1 c.3122T > C; p.(Met1041Thr) mutation from a Dutch genetically isolated population in which the CRB1 gene was originally identified. The authors evaluated medical records, analyzed a questionnaire, and performed a comprehensive ophthalmic examination, including optical coherence tomography. Results: Mean follow-up was 19 years (range 0-45 years, SD 15 years). With aging, patients showed progressive visual decline, deterioration of visual fields, increasing narrowing of the anterior chamber, increased prevalence of cataract, and an increase in the amount of intraretinal pigmentations. Fifty percent of patients had a visual acuity of ≤0.3 at Age 18 and of ≤0.1 at Age 35. Electroretinogram responses were severely reduced or absent already at a young age and optical coherence tomography showed increased retinal thickness with often cystoid maculopathy at young age, and thinning of the retina and disorientation of the photoreceptor layer in the late stages. The clinical course showed considerable interindividual variability, but intraindividual similarity between both eyes was the rule. Conclusion: The wide and variable clinical spectrum in patients with the same CRB1 mutation supports the hypothesis that the CRB1 type autosomal recessive retinitis pigmentosa-phenotype is modulated by other factors. The clinical variability will make it harder to evaluate the effect of (upcoming) therapies for retinitis pigmentosa, although because of the intraindividual similarity between both eyes, the contralateral eye can be used as an excellent internal control.

AB - Purpose: To examine the long-term clinical course and variability in a large pedigree segregating CRB1 type autosomal recessive retinitis pigmentosa. Methods: An observational case study of 30 patients with CRB1 type autosomal recessive retinitis pigmentosa, homozygous for the CRB1 c.3122T > C; p.(Met1041Thr) mutation from a Dutch genetically isolated population in which the CRB1 gene was originally identified. The authors evaluated medical records, analyzed a questionnaire, and performed a comprehensive ophthalmic examination, including optical coherence tomography. Results: Mean follow-up was 19 years (range 0-45 years, SD 15 years). With aging, patients showed progressive visual decline, deterioration of visual fields, increasing narrowing of the anterior chamber, increased prevalence of cataract, and an increase in the amount of intraretinal pigmentations. Fifty percent of patients had a visual acuity of ≤0.3 at Age 18 and of ≤0.1 at Age 35. Electroretinogram responses were severely reduced or absent already at a young age and optical coherence tomography showed increased retinal thickness with often cystoid maculopathy at young age, and thinning of the retina and disorientation of the photoreceptor layer in the late stages. The clinical course showed considerable interindividual variability, but intraindividual similarity between both eyes was the rule. Conclusion: The wide and variable clinical spectrum in patients with the same CRB1 mutation supports the hypothesis that the CRB1 type autosomal recessive retinitis pigmentosa-phenotype is modulated by other factors. The clinical variability will make it harder to evaluate the effect of (upcoming) therapies for retinitis pigmentosa, although because of the intraindividual similarity between both eyes, the contralateral eye can be used as an excellent internal control.

KW - Clinical course

KW - CRB1

KW - Phenotype

KW - Retinitis pigmentosa

KW - RP12

KW - Variability

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U2 - 10.1097/IAE.0000000000001127

DO - 10.1097/IAE.0000000000001127

M3 - Article

VL - 37

SP - 161

EP - 172

JO - Retina-the journal of retinal and vitreous diseases

JF - Retina-the journal of retinal and vitreous diseases

SN - 0275-004X

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ER -