Predominantly Cone-System Dysfunction as Rare Form of Retinal Degeneration in Patients With Molecularly Confirmed Bardet-Biedl Syndrome

Scheidecker, Sophie; Hull, Sarah; Perdomo, Yaumara; Studer, Fouzia; Pelletier, Valérie; Muller, Jean; Schaefer, Élise; Defoort‐Dhellemmes, Sabine; Drumare, Isabelle; Holder, Graham E.; Hamel, Christian; Webster, Andrew R.; Moore, Anthony T.; Puech, Bernard; Dollfus, Hélène

doi:10.1016/j.ajo.2015.05.007

Cited by 30 publications

(26 citation statements)

References 14 publications

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“…The Y-shaped metacarpian has been already correlated with mutation in BBS17/LZTFL1 (Schaefer et al, 2014) that is now extended to IFT27 . One can notice also that 2 patients had cone-rod dystrophy (our patient and family 2), a rare condition already described in BBS (Scheidecker et al, 2015). These features show the clinical variability associated to IFT27 mutations from severe lethal forms to classical BBS that might be revised when new patients will be described in the future.…”

Section: Discussionsupporting

confidence: 60%

Identification and Characterization of Known Biallelic Mutations in the IFT27 (BBS19) Gene in a Novel Family With Bardet-Biedl Syndrome

et al. 2019

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Bardet-Biedl syndrome (BBS; MIM 209900) is a rare ciliopathy characterized by retinitis pigmentosa, postaxial polydactyly, obesity, hypogonadism, cognitive impairment and kidney dysfunction. Mutations in 22 BBS genes have been identified to cause the disease. We report a family with typical BBS features (retinitis pigmentosa, postaxial polydactyly, obesity, cognitive impairment, and atrioventricular septal defect) mutated in IFT27/BBS19. IFT27 is part of the Intraflagellar transport (IFT), a bidirectional mechanism allowing the protein motility within the cilia. Using whole exome sequencing, two compound heterozygous mutations were found in the proband (NM_006860.4:c.[104A > G];[349+1G > T], p.[Tyr35Cys];[?]) consistent with the expected autosomal recessive inheritance mode. These two mutations have already been reported but independently in other families and lacking either familial segregation or functional validation. This is the third report of IFT27 mutations in BBS patients confirming IFT27 as a BBS gene (BBS19). Mutations in IFT genes (IFT27, IFT172 and IFT74) confirm the IFT-pathway as a pathomechanism for BBS.

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Section: Discussionsupporting

confidence: 60%

Identification and Characterization of Known Biallelic Mutations in the IFT27 (BBS19) Gene in a Novel Family With Bardet-Biedl Syndrome

et al. 2019

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“…The BBSome complex is required for ciliary localization and assembly [9]. The recent report of Scheidecker et al [33] functionally characterized the clinical features of the BBS patients with the mutations in the BBS5 gene [33,34]. They found significant macular dystrophy in all patients, which typically presented with central hypofluorescence enclosed by an incessant hyperfluorescent ring on fundus autofluorescence imaging [33].…”

Section: Discussionmentioning

confidence: 99%

“…The recent report of Scheidecker et al [33] functionally characterized the clinical features of the BBS patients with the mutations in the BBS5 gene [33,34]. They found significant macular dystrophy in all patients, which typically presented with central hypofluorescence enclosed by an incessant hyperfluorescent ring on fundus autofluorescence imaging [33]. The splicing mutation might shift the reading frame and probably results in a truncated protein by skipping an exon, leading to loss of functional domains for forming the BBSome protein complex.…”

Section: Discussionmentioning

confidence: 99%

Novel splicing variant c. 208+2T>C inBBS5segregates with Bardet–Biedl syndrome in an Iranian family by targeted exome sequencing

Imani

Cheng

et al. 2019

Bioscience Reports

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Bardet–Biedl syndrome (BBS) is a rare genetically heterogeneous ciliopathy which accompanies retinitis pigmentosa (RP). However, the BBS5 mutation remains unclear in Iranians with BBS. The purpose of study is to evaluate genetic analyses of a BBS Iranian family using targetted exome sequencing (TES). A male 11-year-old proband and three related family members were recruited. Biochemical tests, electrocardiography and visual acuity testing, such as funduscopic, fundus photography (FP), optical coherence tomography (OCT), and standard electroretinography, were conducted. Molecular analysis and high-throughput DNA sequence analysis were performed. The proband was diagnosed with possible BBS based on the presence of three primary features and two secondary features. The TES analysis of the proband with BBS resulted in the identification of a novel, homozygous splicing variant c. 208+2T>C of the BBS5 gene (NM_152384.2) in this Iranian BBS family. This variant was confirmed and was completely co-segregated with the disease in this family by Sanger sequencing. Thus, we report a novel, homozygous splicing site variant c.208+2T>C in the BBS5 gene for the first time in the Iranian family.

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“…The results above further indicate that retinopathy in ciliopathies may be caused by different mechanisms albeit they exhibit similarity and overlap of retinal phenotypes, and clinical intervention in the future should be given based on precise mechanism dissection. It is known that the retinal phenotypes of ciliopathies show large heterogeneity within the same diseases (Scheidecker et al, 2015). For example, it is well known that the BBS syndrome is a genetically heterogeneous disease.…”

Section: Discussionmentioning

confidence: 99%

In vivo phenotypic and molecular characterization of retinal degeneration in mouse models of three ciliopathies

Brun

Obringer

et al. 2019

Experimental Eye Research

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Cilia are highly conserved and ubiquitously expressed organelles. Ciliary defects of genetic origins lead to ciliopathies, in which retinal degeneration (RD) is one cardinal clinical feature. In order to efficiently find and design new therapeutic strategies the underlying mechanism of retinal degeneration of three murine model was compared. The rodent models correspond to three emblematic ciliopathies, namely: Bardet-Biedl Syndrome (BBS), Alström Syndrome (ALMS) and CEP290-mediated Leber Congenital Amaurosis (LCA). Scotopic rodent electroretinography (ERG) was used to test the retinal function of mice, Transmitted Electron microscopy (T.E.M) was performed to assess retinal structural defects and real-time PCR for targeted genes was used to monitor the expression levels of the major apoptotic Caspase-related pathways in retinal extracts to identify pathological pathways driving the RD in order to identify potential therapeutic targets. We found that BBS and CEP290-mediated LCA mouse models exhibit perinatal retinal degeneration associated with rhodopsin mislocalization in the photoreceptor and the induction of an Endoplasmic Reticulum (ER) stress. On the other hand, the tested ALMS mouse model, displayed a slower degeneration phenotype, with no Rhodopsin mislocalization nor ER-stress activity. Our data points out that behind the general phenotype of vision loss associated with these ciliopathies, the mechanisms and kinetics of disease progression are different.

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Predominantly Cone-System Dysfunction as Rare Form of Retinal Degeneration in Patients With Molecularly Confirmed Bardet-Biedl Syndrome

Cited by 30 publications

References 14 publications

Identification and Characterization of Known Biallelic Mutations in the IFT27 (BBS19) Gene in a Novel Family With Bardet-Biedl Syndrome

Identification and Characterization of Known Biallelic Mutations in the IFT27 (BBS19) Gene in a Novel Family With Bardet-Biedl Syndrome

Novel splicing variant c. 208+2T>C inBBS5segregates with Bardet–Biedl syndrome in an Iranian family by targeted exome sequencing

In vivo phenotypic and molecular characterization of retinal degeneration in mouse models of three ciliopathies

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Predominantly Cone-System Dysfunction as Rare Form of Retinal Degeneration in Patients With Molecularly Confirmed Bardet-Biedl Syndrome

Cited by 30 publications

References 14 publications

Identification and Characterization of Known Biallelic Mutations in the IFT27 (BBS19) Gene in a Novel Family With Bardet-Biedl Syndrome

Identification and Characterization of Known Biallelic Mutations in the IFT27 (BBS19) Gene in a Novel Family With Bardet-Biedl Syndrome

Novel splicing variant c. 208+2T&gt;C inBBS5segregates with Bardet–Biedl syndrome in an Iranian family by targeted exome sequencing

In vivo phenotypic and molecular characterization of retinal degeneration in mouse models of three ciliopathies

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Novel splicing variant c. 208+2T>C inBBS5segregates with Bardet–Biedl syndrome in an Iranian family by targeted exome sequencing