Exome sequencing in a Romanian <scp>Bardet‐Biedl</scp> syndrome cohort revealed an overabundance of causal <scp><i>BBS12</i></scp> variants

Khan, Sheraz; Focșa, Ina Ofelia; Budişteanu, Magdalena; Socolovschi, Cristina; Nedelea, Florina; Bohîlțea, Laurențiu Camil; Caba, Lavinia; Butnariu, Lăcrămioara Ionela; Pânzaru, Monica; Rusu, Cristina; Jurcă, Claudia; Chirita-Emandi, Adela; Bănescu, Claudia; Abbas, Wasim; Sadeghpour, Azita; Baig, Shahid Mahmood; Bălgrădean, Mihaela; Davis, Erica E.

doi:10.1002/ajmg.a.63322

Cited by 3 publications

(3 citation statements)

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“…To date, 28 genes have been reported to be associated with BBS phenotypes ( Niederlova et al, 2019 ; Gnanasekaran et al, 2023 ; Khan et al, 2023 ). Unlike Caucasian patients with higher proportions of BBS1 and BBS10 ( Niederlova et al, 2019 ; Melluso et al, 2023 ), we noted that BBS7 was the prominent genotype, followed by BBS2 , BBS10 , BBS12 , and BBS1 in these Chinese seies.…”

Section: Discussionmentioning

confidence: 99%

“…BBS is a ciliopathy and has been shown to be closely related to dysfunction of immotile cilia. To date, 28 genes have been reported to be associated with the BBS phenotypes, including 2 candidate genes ( SCLT1 and SCAPER ) and 2 contributors ( NPHP1 and TTC21B ) ( Niederlova et al, 2019 ; Khan et al, 2023 ; Gnanasekaran et al, 2023 ). In comparison, pathogenic variants in the BBS genes involved in encoding the BBSome complex, including BBS1 (OMIM 209901), BBS2 (OMIM 606151), BBS4 (OMIM 600374), BBS5 (OMIM 603650), BBS7 (OMIM 607590), BBS8/ TTC8 (OMIM 615985), and BBS9/PTHB1 (OMIM 607968), were the most common, followed by BBS genes involved in encoding BBSome complex “chaperone-like” proteins, including BBS6/ MKKS (OMIM 604896), BBS10 (OMIM 610148) , and BBS12 (OMIM 610683) ( Seongjin et al, 2009 ; Dai et al, 2022 ; Melluso et al, 2023 ).…”

Section: Introductionmentioning

confidence: 99%

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

Xin-Yi,

Yang-Li,

Ling-Hui

2023

Front. Genet.

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Objective: To analyze the phenotypes, genotypes, and the relationship of phenotypes and genotypes for Chinese patients with Bardet-Biedl syndrome (BBS).Methods: The Chinese Wanfang and Weipu data, and PubMed were searched up to December 2022. Patients with detailed clinical feature data were involved in the analysis.Results: A total of 153 Chinese patients, including 87 males, 53 females, and 12 unknown, were enrolled. Their ages ranged from 1.2 to 44 years old with a mean of 16.70 ± 9.90 years old. Among these patients, 80 (52.29%) were reported by ophthalmologists, and only 24 (15.68%) reported by pediatricians. Most patients (132/137, 96.35%) had visual problems; 131/153 (85.62%) had polydactyly; 124/132 (93.93%) were overweight or obese; 63/114 (55.26%) had renal abnormalities; kidney dysfunction was found in 33 (21.57%); 83/104 (79.81%) had hypogonadism and/or genital hypoplasia; and 111/136 (81.62%) had mental retardation. In this series, genetic analysis was performed in 90 (58.82%) patients, including 22 BBS7 (24.71%), 20 BBS2 (22.73%), and 10 BBS10 (11.24%) patients. Moreover, 11 fetuses were diagnosed prenatally in the last 4 years except for one patient in 2004 year. It was noted that BBS7 had higher penetrance. BBS2 had higher hearing impairment and lower renal abnormality penetrance. BBS10 also had lower renal abnormality penetrance as well.Conclusion: Misdiagnosis or miss diagnosis of BBS may be common in China. In patients with polydactyly, visual impairment, obesity, renal abnormalities, hypogonadism, and mental retardation, or in fetuses with polydactyly and/or renal abnormalities, BBS should be considered in the differential diagnosis. Other deformities should be evaluated carefully and genetic analysis should be performed as early as possible.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Xin-Yi,

Yang-Li,

Ling-Hui

2023

Front. Genet.

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“…Surprisingly, we found that BBS7 is the most common gene (5/11) involved in Chinese patients, followed by BBS2 and IFT74, inconsistent with other studies. Khan et al 14…”

Section: Discussionmentioning

confidence: 99%

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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Bardet‐Biedl syndrome: A focus on genetics, mechanisms and metabolic dysfunction

Tomlinson

2024

Diabetes Obesity Metabolism

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Bardet‐Biedl syndrome (BBS) is a rare, monogenic, multisystem disorder characterized by retinal dystrophy, renal abnormalities, polydactyly, learning disabilities, as well as metabolic dysfunction, including obesity and an increased risk of type 2 diabetes. It is a primary ciliopathy, and causative mutations in more than 25 different genes have been described. Multiple cellular mechanisms contribute to the development of the metabolic phenotype associated with BBS, including hyperphagia as a consequence of altered hypothalamic appetite signalling as well as alterations in adipocyte biology promoting adipocyte proliferation and adipogenesis. Within this review, we describe in detail the metabolic phenotype associated with BBS and discuss the mechanisms that drive its evolution. In addition, we review current approaches to the metabolic management of patients with BBS, including the use of weight loss medications and bariatric surgery. Finally, we evaluate the potential of targeting hypothalamic appetite signalling to limit hyperphagia and induce clinically significant weight loss.

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Exome sequencing in a Romanian Bardet‐Biedl syndrome cohort revealed an overabundance of causal BBS12 variants

Cited by 3 publications

References 88 publications

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

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

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

Bardet‐Biedl syndrome: A focus on genetics, mechanisms and metabolic dysfunction

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