Mutation profile of <scp>Bardet‐Biedl</scp> syndrome patients from India: Implicative role of multiallelic rare variants and oligogenic inheritance pattern

Gnanasekaran, Harshavardhini; Chandrasekhar, Sathya Priya; Kandeeban, Suganya; Periyasamy, Porkodi; Bhende, Muna; Khetan, Vikas; Gupta, Neerja; Kabra, Madhulika; Namboothri, Sheela; Sen, Parveen; Sripriya, Sarangapani

doi:10.1111/cge.14398

Cited by 5 publications

(4 citation statements)

References 71 publications

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“…Their BMI ranged from 11.94 to 48.89 kg/m 2 with a mean BMI of 29.08 ± 6.40 kg/m 2 among 102 patients. The incidence of overweight and obesity in our series (123/132, 93.18%) was higher than those in Gnanasekaran et al (2023) (77/108, 71.30%; χ 2 = 7.375, p = 0.007), Beales et al (1999) (78/102, 76.47%; χ 2 = 14.874, p < 0.001), and Mujahid et al (2018) (101/131, 77.10%; χ 2 = 15.084, p < 0.001) reports, but had no significant difference form and Moore et al (2005) (45/45, 100%; p = 0.205) report. It was notable that hypertension was reported in 32 patients (20.91%).…”

Section: Resultscontrasting

confidence: 68%

“…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: Resultscontrasting

confidence: 68%

Section: Discussionmentioning

confidence: 99%

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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“…A phenomenon that could be explained by BBSome chaperone protein is involved in the early synthesis of BBSome [ 76 ]. 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 ].…”

Section: Discussionmentioning

confidence: 91%

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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Familial osteochondrodysplastic and cardiomyopathic syndrome in Chianina cattle

Jacinto,

Ogundipe,

Benazzi

et al. 2024

Veterinary Internal Medicne

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BackgroundSkeletal dysplasia encompasses a heterogeneous group of genetic disorders characterized by an abnormal development of bones, joints, and cartilage. Two Chianina half‐sibling calves from consanguineous mating with congenital skeletal malformations and cardiac abnormalities were identified.Hypothesis/ObjectivesTo characterize the disease phenotype, to evaluate its genetic cause, and to determine the prevalence of the deleterious alleles in the Chianina population.AnimalsTwo affected calves, their parents and 332 Chianina bulls.MethodsThe affected animals underwent clinicopathological investigation. Whole‐genome sequencing trio‐approach and PCR‐based assessment of the frequency of TDP‐glucose 4,6‐dehydratase (TGDS) and laminin subunit alpha 4 (LAMA4) alleles were performed.ResultsThe cases presented with retarded growth, poor nutritional status associated with muscular atrophy and angular deformities of the hindlimbs. Radiologic examination identified generalized osteopenia and shortening of the limb long bones. Necropsy showed osteochondrodysplastic limbs and dilatation of the heart right ventricle. On histological examination, the physeal cartilages were characterized by multifocal mild to moderate loss of the normal columnar arrangement of chondrocytes. Osteopenia also was observed. Genetic analysis identified a missense variant in TGDS and a splice‐site variant in LAMA4, both of which were homozygous in the 2 cases. Parents were heterozygous and allele frequency in the Chianina population for the TGDS variant was 5% and for the LAMA4 variant was 2%.Conclusions and Clinical ImportanceGenetic findings identified 2 potentially pathogenic alleles in TGDS and LAMA4, but no clear mode of inheritance could be determined.

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Mutation profile of Bardet‐Biedl syndrome patients from India: Implicative role of multiallelic rare variants and oligogenic inheritance pattern

Cited by 5 publications

References 71 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

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

Familial osteochondrodysplastic and cardiomyopathic syndrome in Chianina cattle

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