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Phenotypic expression of Bardet-Biedl syndrome in patients homozygous for the common M390R mutation in the BBS1 gene.
Vision Res. 2012 Dec 15; 75:77-87.VR

Abstract

PURPOSE

To characterize the phenotype of Bardet-Biedl syndrome (BBS) patients homozygous for the BBS1 M390R mutation.

METHODS

Three patients [PT1, F, 27 years old (yo) at last examination, 14-year follow-up (F/U) PT2, F, 15-yo PT3, M, 15-yo, both 1-year F/U] underwent eye exams, Goldmann visual fields (GVFs), dark- (DA) and light-adapted (LA) electroretinograms (ERGs), spectral domain optical coherence tomography (SD-OCT) and fundus autofluorescence (FAF). Vision and systemic history were also collected.

RESULTS

All patients had night blindness, hyperopic astigmatism, ptosis or mild blepharospasm, foot polydactyly, 5th finger clinodactyly, history of headaches, and variable, diet-responsive obesity. Two had asthma, PT1 was developmentally delayed, PT2 had Asperger-like symptoms, and PT3 had normal cognition. At age 14, acuity was 20/100 in PT1, who had nystagmus since age 2, 20/40 in PT2 and 20/30 in PT3. By 27yo PT1 progressed to 20/320, by 15 yo PT2 was 20/60 and PT3 remained stable. PT1 had well preserved peripheral GVFs, with minimal progression over 10 years of F/U. PT2 and PT3 presented with ring scotomas and I4e<5°. All patients had severe generalized visual sensitivity depression. ERGs were consistently recordable (also rod ERG in PT3 after 60 min DA), but progressed to non-recordable in PT1. Mixed DA ERGs exhibited electronegativity. In PT3, this was partly due to a bleaching effect during bright-flash DA averaging, partly to ON≫OFF LA response compromise. PT2 and 3 had, on SD-OCTs, generalized macular thinning, normal retinal lamination, and widespread photoreceptor outer/inner segment attenuation except foveally, and multiple rings of abnormal FAF configuring a complex bull's eye-pattern. PT1 had macular atrophy. All patients also had peripapillary nerve fiber layer thickening.

CONCLUSIONS

The observed phenotype matches very closely that reported in patients by Azari et al. (IOVS 2006) and in the Bbs1-M390R knock-in mouse model, and expands it to the characterization of important ERG response characteristics that provide insight in the pathogenesis of retinopathy in these patients. Our findings confirm the consistent pathogenicity of the BBS1 M390R mutation.

Authors+Show Affiliations

University of Tennessee Health Science Center, Hamilton Eye Institute, Memphis, TN 38163, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22940089

Citation

Cox, Kyle F., et al. "Phenotypic Expression of Bardet-Biedl Syndrome in Patients Homozygous for the Common M390R Mutation in the BBS1 Gene." Vision Research, vol. 75, 2012, pp. 77-87.
Cox KF, Kerr NC, Kedrov M, et al. Phenotypic expression of Bardet-Biedl syndrome in patients homozygous for the common M390R mutation in the BBS1 gene. Vision Res. 2012;75:77-87.
Cox, K. F., Kerr, N. C., Kedrov, M., Nishimura, D., Jennings, B. J., Stone, E. M., Sheffield, V. C., & Iannaccone, A. (2012). Phenotypic expression of Bardet-Biedl syndrome in patients homozygous for the common M390R mutation in the BBS1 gene. Vision Research, 75, 77-87. https://doi.org/10.1016/j.visres.2012.08.005
Cox KF, et al. Phenotypic Expression of Bardet-Biedl Syndrome in Patients Homozygous for the Common M390R Mutation in the BBS1 Gene. Vision Res. 2012 Dec 15;75:77-87. PubMed PMID: 22940089.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Phenotypic expression of Bardet-Biedl syndrome in patients homozygous for the common M390R mutation in the BBS1 gene. AU - Cox,Kyle F, AU - Kerr,Natalie C, AU - Kedrov,Marina, AU - Nishimura,Darryl, AU - Jennings,Barbara J, AU - Stone,Edwin M, AU - Sheffield,Val C, AU - Iannaccone,Alessandro, Y1 - 2012/08/24/ PY - 2012/07/07/received PY - 2012/08/07/revised PY - 2012/08/08/accepted PY - 2012/9/4/entrez PY - 2012/9/4/pubmed PY - 2013/5/31/medline SP - 77 EP - 87 JF - Vision research JO - Vision Res VL - 75 N2 - PURPOSE: To characterize the phenotype of Bardet-Biedl syndrome (BBS) patients homozygous for the BBS1 M390R mutation. METHODS: Three patients [PT1, F, 27 years old (yo) at last examination, 14-year follow-up (F/U) PT2, F, 15-yo PT3, M, 15-yo, both 1-year F/U] underwent eye exams, Goldmann visual fields (GVFs), dark- (DA) and light-adapted (LA) electroretinograms (ERGs), spectral domain optical coherence tomography (SD-OCT) and fundus autofluorescence (FAF). Vision and systemic history were also collected. RESULTS: All patients had night blindness, hyperopic astigmatism, ptosis or mild blepharospasm, foot polydactyly, 5th finger clinodactyly, history of headaches, and variable, diet-responsive obesity. Two had asthma, PT1 was developmentally delayed, PT2 had Asperger-like symptoms, and PT3 had normal cognition. At age 14, acuity was 20/100 in PT1, who had nystagmus since age 2, 20/40 in PT2 and 20/30 in PT3. By 27yo PT1 progressed to 20/320, by 15 yo PT2 was 20/60 and PT3 remained stable. PT1 had well preserved peripheral GVFs, with minimal progression over 10 years of F/U. PT2 and PT3 presented with ring scotomas and I4e<5°. All patients had severe generalized visual sensitivity depression. ERGs were consistently recordable (also rod ERG in PT3 after 60 min DA), but progressed to non-recordable in PT1. Mixed DA ERGs exhibited electronegativity. In PT3, this was partly due to a bleaching effect during bright-flash DA averaging, partly to ON≫OFF LA response compromise. PT2 and 3 had, on SD-OCTs, generalized macular thinning, normal retinal lamination, and widespread photoreceptor outer/inner segment attenuation except foveally, and multiple rings of abnormal FAF configuring a complex bull's eye-pattern. PT1 had macular atrophy. All patients also had peripapillary nerve fiber layer thickening. CONCLUSIONS: The observed phenotype matches very closely that reported in patients by Azari et al. (IOVS 2006) and in the Bbs1-M390R knock-in mouse model, and expands it to the characterization of important ERG response characteristics that provide insight in the pathogenesis of retinopathy in these patients. Our findings confirm the consistent pathogenicity of the BBS1 M390R mutation. SN - 1878-5646 UR - https://www.unboundmedicine.com/medline/citation/22940089/Phenotypic_expression_of_Bardet_Biedl_syndrome_in_patients_homozygous_for_the_common_M390R_mutation_in_the_BBS1_gene_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0042-6989(12)00255-6 DB - PRIME DP - Unbound Medicine ER -