Characteristics of genotype and phenotype in Chinese patients with Bardet–Biedl syndrome

Tao, Tianchang; Wang, Lei; Weihua, Chong; Yang, Liping; Li, Genlin

doi:10.1007/s10792-020-01415-3

Cited by 10 publications

(12 citation statements)

References 51 publications

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“…The mutation spectrum is comparable to that of other recent studies [35,65,66], and 51 different variants were observed, either (apparent) homozygous or two (compound) heterozygous variants found in 12 different genes (Supplementary Tables S1 and S2). Of these, 11 variants have never been reported before and deserve further discussion.…”

Section: Discussionsupporting

confidence: 83%

Ophthalmic and Genetic Features of Bardet Biedl Syndrome in a German Cohort

Nasser

Kohl

Kurtenbach

et al. 2022

Genes

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The aim of this study was to characterize the ophthalmic and genetic features of Bardet Biedl (BBS) syndrome in a cohort of patients from a German specialized ophthalmic care center. Sixty-one patients, aged 5–56 years, underwent a detailed ophthalmic examination including visual acuity and color vision testing, electroretinography (ERG), visually evoked potential recording (VEP), fundus examination, and spectral domain optical coherence tomography (SD-OCT). Adaptive optics flood illumination ophthalmoscopy was performed in five patients. All patients had received diagnostic genetic testing and were selected upon the presence of apparent biallelic variants in known BBS-associated genes. All patients had retinal dystrophy with morphologic changes of the retina. Visual acuity decreased from ~0.2 (decimal) at age 5 to blindness 0 at 50 years. Visual field examination could be performed in only half of the patients and showed a concentric constriction with remaining islands of function in the periphery. ERG recordings were mostly extinguished whereas VEP recordings were reduced in about half of the patients. The cohort of patients showed 51 different likely biallelic mutations—of which 11 are novel—in 12 different BBS-associated genes. The most common associated genes were BBS10 (32.8%) and BBS1 (24.6%), and by far the most commonly observed variants were BBS10 c.271dup;p.C91Lfs*5 (21 alleles) and BBS1 c.1169T>G;p.M390R (18 alleles). The phenotype associated with the different BBS-associated genes and genotypes in our cohort is heterogeneous, with diverse features without genotype–phenotype correlation. The results confirm and expand our knowledge of this rare disease.

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Section: Discussionsupporting

confidence: 83%

Ophthalmic and Genetic Features of Bardet Biedl Syndrome in a German Cohort

Nasser

Kohl

Kurtenbach

et al. 2022

Genes

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“…Attempts to establish a genotype-phenotype correlation of the various BBS subtypes have been challenging due to the high heterogeneity displayed by the disease and the relatively small cohorts from which phenotypical data has been gathered. [12][13][14][15][16][17][18][19] Nevertheless, we sought to collect detailed clinical information from our Puerto Rican BBS cohort, since it has been suggested that the island might have one of the highest BBS prevalences, globally.…”

Section: Discussionmentioning

confidence: 99%

“…2 Regional and ethnic genotypic and phenotypic variations have been previously suggested. [12][13][14][15][16][17][18][19] Most of the studies that have explored genotype-phenotype relationships have failed to establish true correlations, yet certain trends have been observed. For instance, Castro-Sanchez et al 19 found that, within their Spanish cohort, BBS1 patients seemed to display an overall milder ocular and systemic phenotype than did patients with BBS6, BBS10, or BBS12.…”

Section: Introductionmentioning

confidence: 99%

A Genotype–Phenotype Analysis of the Bardet–Biedl Syndrome in Puerto Rico

Guardiola

Ramos

Izquierdo

et al. 2021

OPTH

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Background: Bardet-Biedl syndrome is a complex heterogeneous ciliopathy caused by genetic mutations. Although establishing genotype-phenotype correlations has been challenging, some regional variations have been previously reported. Due to its relative geographic isolation, Puerto Rico has a greater prevalence of Bardet-Biedl syndrome than do other regions. We sought to characterize the most frequent genotypic variations in a local cohort of Bardet-Biedl syndrome patients and report any genotypic-phenotypic trends. Methods: Twenty-seven patients from an ophthalmology clinic in Puerto Rico with genetically confirmed Bardet-Biedl syndrome took a questionnaire inquiring about their most common symptoms. Ophthalmological information was obtained from patient records. The frequencies of the genotypic variations and symptoms were calculated. Results: In the study population, BBS1 was the most prevalent mutated gene, followed by BBS7. In the BBS1 group, we found homozygotes for c.1169T>G (p.Met390Arg) and c.1645G>T (p. Glu549*), and compound heterozygotes for c.1169T>G (p.Met390Arg) and c.1645G>T (p. Glu549*), with one patient having c.1645G>T (p.Glu549*) and c.432+1G>A (splice donor). All the BBS7 patients were homozygous for c.632C>T (p.Thr211Ile). Compared to BBS7, we found that BBS1 patients generally had a milder ocular and systemic phenotype. However, when analyzing different BBS1 variants, patients with mutations in c.1645G>T (p.Glu549*), both compound heterozygous and homozygous, had more severe systemic phenotypes, overall. Conclusion:Our study was the first detailed genotype-phenotype analysis of the Bardet-Biedl syndrome in Puerto Rico. Genetic mutations in BBS1 and BBS7 seem to be the most common culprits behind Bardet-Biedl syndrome in this population. Although patients diagnosed with BBS1 are likely to display milder systemic features, this was not the case with our BBS1 patients having the c.1645G>T (p.Glu549*) mutation. Further studies should focus on the c.1645G>T (p.Glu549*) mutation's impact on the BBS1 gene and protein product.

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“…Additionally, one study on patients with the same geographic origin also reported a BBS patient (P04) with compound heterozygous mutations in BBS10 , c.539G>A; p.G180E and c.602G>A; p.C201Y, and P04 who started experiencing reduced vision at the age of 16. 12 It is noteworthy that they carried the same missense mutation and exhibited inconsistent ocular phenotypes. Compared with P04, who harboured two missense mutations in the BBS10 gene, earlier onset of visual impairment and developmental delay were found in F3–II:1, who harboured one missense mutation and one nonsense mutation in BBS10 .…”

Section: Discussionmentioning

confidence: 99%

Novel mutations in BBS genes and clinical characterization of Chinese families with Bardet–Biedl syndrome

Tao

Liu

Wang

et al. 2022

European Journal of Ophthalmology

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Purpose Bardet–Biedl syndrome (BBS) is a rare autosomal-recessive inherited disorder characterized by multisystem anomalies. The objective of this study was to detect and analyse pathogenic variants in four Chinese families with BBS. Methods Comprehensive clinical examinations were performed to investigate and evaluate the phenotypes of the affected individuals from four families. Genomic DNA was extracted from peripheral blood. Next-generation sequencing (NGS) was performed for four families, and the presence of pathogenic variants was confirmed via Sanger sequencing. Results There were two males and three females with a mean age of 16.00 years. All probands displayed the primary clinical features of BBS. Mutation screening demonstrated four novel mutations: c.613C>T; p.Q205* in the BBS5 gene, c.1391C>G; p.S464* in the BBS10 gene, and c.155delC; p.S52* and c.1584T>G; p.Y528* in the BBS12 gene. Two previously reported mutations were also identified, including c.534 + 1G>T in the BBS2 gene and c.539G>A; p.G180E in the BBS10 gene. The bioinformatic analysis revealed that all the detected mutations in BBS genes were disease causing. Conclusions This study identified four novel BBS gene mutations in these Chinese families and further expanded the genotypic spectrum of BBS, thus contributing to the literature and understanding of this multisystem disease.

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Characteristics of genotype and phenotype in Chinese patients with Bardet–Biedl syndrome

Cited by 10 publications

References 51 publications

Ophthalmic and Genetic Features of Bardet Biedl Syndrome in a German Cohort

Ophthalmic and Genetic Features of Bardet Biedl Syndrome in a German Cohort

A Genotype–Phenotype Analysis of the Bardet–Biedl Syndrome in Puerto Rico

Novel mutations in BBS genes and clinical characterization of Chinese families with Bardet–Biedl syndrome

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