Review of the phenotypes and genotypes of Bardet-Biedl syndrome from China

Xin-Yi, Zou; Yang-Li, Dai; Ling-Hui, Zeng

doi:10.3389/fgene.2023.1247557

Cited by 8 publications

(5 citation statements)

References 101 publications

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“…This was comparable to our study. However, in our study, the latter subgroups also showed a multitude of structural anomalies with a higher frequency than in other studies (40), indicating the high sensitivity of the applied US methods (44). Consistent with recent studies (9,10,11), our results support the milder renal involvement in patients with BBS1 mutations.…”

Section: Renal Involvementsupporting

confidence: 92%

“…The distribution of pathogenic variants in our BBS cohort was similar to other recent studies from Europe and the USA with a predominance of pathogenic variations in BBS1 and BBS10 (9,10,11), but differed from a study in China, where the majority of patients were affected by mutations in BBS2 and BBS7 (40). Moreover, we noted an accumulation of the hot spot mutations c.271dupT (p.Cys91Leufs*5) in BBS10 and c.1169T > G (p.Met390Arg) in BBS1.…”

Section: Study Cohortsupporting

confidence: 85%

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Ultrasound evaluation of kidney and liver involvement in Bardet-Biedl syndrome

Cetiner,

Finkelberg,

Schiepek

et al. 2024

Preprint

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Background Bardet-Biedl syndrome (BBS) is a rare autosomal-recessive ciliopathy with pathogenic variants in at least 26 BBS genes. It affects multiple organs including kidney and liver, however, organ involvement differs widely regarding extent and time of first manifestation. Structural renal anomalies are an early feature with a frequency of > 50% and end-stage kidney disease (ESKD) cumulates to 25% in adolescence. Early-onset hyperphagia-associated obesity is another major symptom and contributes to liver pathology, presenting as steatosis/fibrosis. Aim of this study is the evaluation of high-end ultrasound (US) technologies including shear wave elastography (SWE), dispersion (SWD), and attenuation imaging (ATI) in BBS patients regarding their potential to discriminate liver and kidney tissue pathology at an early stage. Materials and Methods Patients with genetically proven BBS were recruited from the University Children’s Hospital of Essen and from BBS patient days hosted in Germany. Acute illness was an exclusion criterion. Clinical and laboratory data were extracted from patients’ digital records or medical letters. Results 49 BBS patients (24/49 male; aged 1.1–51.0 years, mean 17.8 years) were included in the study. Mean body weight (SDS 2.13 ± 1.33) and BMI (SDS 2.64 ± 1.18) were increased. Structural kidney abnormalities (dysplasia, cysts) were present in 75% (36/48) and persistent fetal lobulation in 44% (21/48). Renal function was impaired in 27% (13/49) and 3/13 had ESKD (kidney transplantation (n = 2), hemodialysis (n = 1)). Elevation of liver enzymes was detected in 38% (16/42). In 51% (25/49) ATI of liver tissue was increased, indicating hepatic steatosis, and correlated with BMI SDS, liver size, and enzymes. SWE was elevated in 61% (30/49) suggesting hepatic fibrosis and was associated with BMI and GGT. Patients with pathogenic variants in BBS10 showed a tendency towards higher ATI and reduced GFR, and had significantly higher BMI SDS. Conclusions We detected abnormalities of the kidney and liver in a higher percentage of BBS patients than previously reported, indicating a high sensitivity of the evaluated US applications. ATI detected liver pathology early (partially prior to liver enzymes) and revealed differences related to the affected genes. Evidence of tissue pathology at an early stage may improve diagnostics and the evaluation of therapeutic approaches.

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Section: Renal Involvementsupporting

confidence: 92%

Section: Study Cohortsupporting

confidence: 85%

Ultrasound evaluation of kidney and liver involvement in Bardet-Biedl syndrome

Cetiner,

Finkelberg,

Schiepek

et al. 2024

Preprint

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“…Perea-Romero et al 15 reported that BBS1 alleles, found in 42% of 77 Spanish families, were the most represented in their cohort. Mary et al 16 17 suggesting a possible founder effect in this ethnicity. Defects in other genes involved in BBS had not been detected in our series.…”

Section: Reported 17mentioning

confidence: 76%

Phenotypic and genotypic analysis of 11 fetal cases with Bardet–Biedl syndrome

Yu,

Liu,

Zhen

et al. 2024

Prenatal Diagnosis

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ObjectiveTo present the prenatal sonographic features and genomic spectrum of pregnancies with fetal Bardet–Biedl syndrome (BBS).MethodsThis was a retrospective study of 11 cases with BBS diagnosed by prenatal ultrasound and confirmed by genetic testing. Clinical and laboratory data were collected and reviewed for these cases, including maternal demographics, prenatal sonographic findings, molecular testing sequencing results, and pregnancy outcomes.ResultsAll cases had unremarkable first‐trimester ultrasound scans without reporting limb malformations. All had second‐trimester abnormal ultrasounds: postaxial polydactyly in nine cases (9/11), renal abnormalities in seven (7/11), reduced amniotic fluid volume in two (2/11), central nervous system anomalies in two (2/11), and ascites in three (3/11). Ten fetuses presented with at least two‐system anomalies, and one (Case 11) presented with only postaxial polydactyly. Variants were detected in five genes, including BBS2, ARL6/BBS3, BBS7, CEP290/BBS14 and IFT74/BBS22. Ten pregnancies were terminated in the second trimester, while one continued to term.ConclusionEnlarged hyperechogenic kidneys and postaxial polydactyly are the two most common sonographic features of fetal BBS. Prenatal diagnosis of BBS can be done with ultrasound and genetic testing although the diagnosis may be made in the second trimester.

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“…What is worth noting is that polydactyly and renal cysts were found in three patients during fetal life by pregnancy examination, but were ignored and not diagnosed with BBS until visual problems occurred. Therefore, in fetuses with polydactyly, genitourinary abnormalities, and/or hydrometrocolpos, BBS should be considered [ 41 ].…”

Section: Resultsmentioning

confidence: 99%

“…The penetrance differences of the primary and secondary symptoms, particularly for renal abnormalities, between the patients with variations in genes encoding chaperonin and BBSome complex were not found in either our cohort or the Indian cohort [ 77 ], suggesting that BBSome function may be entirely dependent on the chaperonin. Zou Xin-Yi et al systematically reviewed the patients with BBS reported from China and found that those with variants in BBS2 had higher hearing impairment, while those with variants in BBS10 had lower renal abnormality penetrance [ 41 ]; Veronika et al revealed that differences in the penetrance of kidney anomalies among patients make biological sense as the causative genes linked to a high frequency of kidney anomalies, which include BBS2 , BBS7 , and BBS9 , encode structurally similar proteins that form the core of the BBSome [ 75 ]. Although this was not observed in our cohort, a comprehensive evaluation of the patients' kidneys should be conducted in the future.…”

Section: Discussionmentioning

confidence: 99%

Molecular and phenotypic characteristics of Bardet-Biedl syndrome in Chinese patients

Gao,

Zhang,

Ding

et al. 2024

Orphanet J Rare Dis

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Background Bardet-Biedl syndrome (BBS) is a type of non-motile ciliopathy. To date, 26 genes have been reported to be associated with BBS. However, BBS is genetically heterogeneous, with significant clinical overlap with other ciliopathies, which complicates diagnosis. Disability and mortality rates are high in BBS patients; therefore, it is urgent to improve our understanding of BBS. Thus, our study aimed to describe the genotypic and phenotypic spectra of BBS in China and to elucidate genotype–phenotype correlations. Methods Twenty Chinese patients diagnosed with BBS were enrolled in this study. We compared the phenotypes of Chinese BBS patients in this study with those from other countries to analyze the phenotypic differences across patients worldwide. In addition, genotype–phenotype correlations were described for our cohort. We also summarized all previously reported cases of BBS in Chinese patients (71 patients) and identified common and specific genetic variants in the Chinese population. Results Twenty-eight variants, of which 10 are novel, in 5 different BBS-associated genes were identified in 20 Chinese BBS patients. By comparing the phenotypes of BBSome-coding genes (BBS2,7,9) with those of chaperonin-coding genes (BBS10,12), we found that patients with mutations in BBS10 and 12 had an earlier age of onset (1.10 Vs. 2.20, p < 0.01) and diagnosis (4.64 Vs. 13.17, p < 0.01), whereas patients with mutations in BBS2, 7, and 9 had a higher body mass index (28.35 Vs. 24.21, p < 0.05) and more vision problems (p < 0.05). Furthermore, in 91 Chinese BBS patients, mutations were predominant in BBS2 (28.89%) and BBS7 (15.56%), and the most frequent variants were in BBS2: c.534 + 1G > T (10/182 alleles) and BBS7: c.1002delT (7/182 alleles), marking a difference from the genotypic spectra of BBS reported abroad. Conclusions We recruited 20 Chinese patients with BBS for genetic and phenotypic analyses, and identified common clinical manifestations, pathogenic genes, and variants. We also described the phenotypic differences across patients worldwide and among different BBS-associated genes. This study involved the largest cohort of Chinese patients with BBS, and provides new insights into the distinctive clinical features of specific pathogenic variants.

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Review of the phenotypes and genotypes of Bardet-Biedl syndrome from China

Cited by 8 publications

References 101 publications

Ultrasound evaluation of kidney and liver involvement in Bardet-Biedl syndrome

Ultrasound evaluation of kidney and liver involvement in Bardet-Biedl syndrome

Phenotypic and genotypic analysis of 11 fetal cases with Bardet–Biedl syndrome

Molecular and phenotypic characteristics of Bardet-Biedl syndrome in Chinese patients

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