Delineating the Spectrum of Genetic Variants Associated with Bardet-Biedl Syndrome in Consanguineous Pakistani Pedigrees

This study aimed to find the molecular basis of Bardet-Biedl syndrome (BBS) in Pakistani consanguineous families. A total of 12 affected families were enrolled. Clinical investigations were performed to access the BBS-associated phenotypes. Whole exome sequencing was conducted on one affected indivi...

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Bibliographic Details
Published in:Genes 2023-02, Vol.14 (2), p.404
Main Authors: Rao, Ali Raza, Nazir, Aamir, Imtiaz, Samina, Paracha, Sohail Aziz, Waryah, Yar Muhammad, Ujjan, Ikram Din, Anwar, Ijaz, Iqbal, Afia, Santoni, Federico A, Shah, Inayat, Gul, Khitab, Baig, Hafiz Muhammad Azhar, Waryah, Ali Muhammad, Antonarakis, Stylianos E, Ansar, Muhammad
Format: Article
Language:English
Subjects:
Amino acids
Bardet-Biedl syndrome
Computer applications
Disease
DNA sequencing
Families & family life
Family medical history
Gene deletion
Genes
Genetic aspects
Genetic diversity
Health sciences
Intellectual disabilities
Methods
Minority & ethnic groups
Nucleotide sequencing
Obesity
Pedigree analysis
Phenotypes
Proteins
Segregation
Siblings
Strabismus
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Summary:This study aimed to find the molecular basis of Bardet-Biedl syndrome (BBS) in Pakistani consanguineous families. A total of 12 affected families were enrolled. Clinical investigations were performed to access the BBS-associated phenotypes. Whole exome sequencing was conducted on one affected individual from each family. The computational functional analysis predicted the variants' pathogenic effects and modeled the mutated proteins. Whole-exome sequencing revealed 9 pathogenic variants in six genes associated with BBS in 12 families. The was the most common BBS causative gene identified in five families (5/12, 41.6%), with one novel (c.1226G>A, p.Gly409Glu) and two reported variants. c.774G>A, Thr259LeuTer21 was the most frequent allele in three families 3/5 (60%). Two variants, c.223C>T, p.Arg75Ter and a novel, c. 252delA, p.Lys85STer39 were detected in the gene. A novel 8bp deletion c.387_394delAAATAAAA, p. Asn130GlyfsTer3 was found in gene. Three known variants were detected in , and genes. Identification of novel likely pathogenic variants in three genes reaffirms the allelic and genetic heterogeneity of BBS in Pakistani patients. The clinical differences among patients carrying the same pathogenic variant may be due to other factors influencing the phenotype, including variants in other modifier genes.
ISSN:2073-4425
2073-4425
DOI:10.3390/genes14020404