Dataset Information

Next-generation sequencing identified novel truncating mutations in BBS9 causing Bardet Biedl syndrome in two Iranian consanguineous families.

ABSTRACT:

Objectives

Bardet-Biedl syndrome (BBS) is an autosomal recessive pleiotropic ciliopathy, which includes multi-organ clinical manifestations. The known genes involved in the development of the disease account for the causality in about 80% of the examined cases.

Materials & methods

We investigated two Iranian unrelated clinically diagnosed BBS patients, using a targeted next-generation sequencing panel consisting of 18 known BBS genes. The detected variants were investigated in the pedigree and studied using in silico tools for their pathogenicity. Patients' phenotypes were also assessed.

Results

Novel homozygous variants were detected in BBS9 gene in each patient, c.2014C>T, p.Gln672Ter and c.673_674insAA, p.Gln225GlnfsX10. The variants were segregated in the corresponding pedigree and were authenticated to obtain enough evidence to be categorized as pathogenic variants.

Conclusion

Patients with truncating mutations in the same gene seem to show similar phenotypic features. Detection of novel and family-specific mutations is typically expected in the genetic hereditary diseases in Iran, which can finally lead to prevent the recurrence of the disease in the consanguineous marriages.

SUBMITTER: Akbaroghli S

PROVIDER: S-EPMC8753002 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Publications

Next-generation sequencing identified novel truncating mutations in BBS9 causing Bardet Biedl syndrome in two Iranian consanguineous families.

Akbaroghli Susan S Kooshavar Daniz D Golchehre Zahra Z Karamzade Arezou A Saberi Mohammad M Alaei Mohammad Reza MR Abbasi Sadegh Masoud M Asadollahi Mostafa M Keramatipour Mohammad M

Iranian journal of child neurology 20220101 1

<h4>Objectives</h4>Bardet-Biedl syndrome (BBS) is an autosomal recessive pleiotropic ciliopathy, which includes multi-organ clinical manifestations. The known genes involved in the development of the disease account for the causality in about 80% of the examined cases.<h4>Materials & methods</h4>We investigated two Iranian unrelated clinically diagnosed BBS patients, using a targeted next-generation sequencing panel consisting of 18 known BBS genes. The detected variants were investigated in the ...[more]

PMID: 35222663

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Project description:BackgroundBardet Biedl Syndrome (BBS) is a rare condition of multi-organ dysfunction with characteristic clinical features of retinal degeneration, truncal obesity, postaxial polydactyly, genital anomaly, intellectual disability and renal dysfunction. It is a hetero-genetic disorder and nineteen BBS genes have been discovered so far.MethodsWhole genome SNP genotyping was performed by using CytoScan® 750 K array (Affymetrix). Subsequently, the segregation of the disease locus in the whole family was carried out by genotyping STS markers within the homozygous interval. Finally, the mutation analysis was performed by Sanger DNA sequencing.ResultsIn the present molecular study a consanguineous Pakistani family, with autosomal recessive BBS, was analyzed. The clinical analysis of affected individuals presented with synpolydactyly, obesity, intellectual disability, renal abnormality and retinitis pigmentosa. The presented phenotype was consistent with the major features of BBS syndrome. Homozygosity mapping identified a common homozygous interval within the known BBS9 locus. Sequence analysis of BBS9/PTHB1 gene revealed a single base deletion of c.299delC (p.Ser100Leufs*24) in exon 4. This frame-shift mutation presumably leads to a 122 amino acid truncated protein with complete loss of its C-terminal PTHB1 domain in combination with a partial loss of the N-terminal PTHB1 domain as well. BBS9/PTHB1 gene mutations have been shown to be associated with BBS syndrome and to the best of our knowledge this study reports the first Pakistani family linked to the BBS9 gene.ConclusionOur molecular findings expand the mutational spectrum of BBS9 gene and also explain the genetic heterogeneity of Pakistan families with BBS syndrome. The growing number of mutations in BBS genes in combination with a detailed phenotypical description of patients will be helpful for genotype-phenotype correlation, targeted genetic diagnosis, prenatal screening and carrier testing of familial and non-familial BBS patients.

Dataset Information

Next-generation sequencing identified novel truncating mutations in BBS9 causing Bardet Biedl syndrome in two Iranian consanguineous families.

Objectives

Materials & methods

Results

Conclusion

Publications

Next-generation sequencing identified novel truncating mutations in BBS9 causing Bardet Biedl syndrome in two Iranian consanguineous families.

Similar Datasets

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