Identification of rare missense variants in the BSN gene co‐segregating with chronic otitis media in a consanguineous Pakistani family

Background Otitis media (OM) is the most frequent and complex middle ear condition with multifactorial etiology including genetic predisposition. OM depicts a variable clinical spectrum, leading to speech, developmental delay, and hearing loss. Here, we report the clinical and genetic findings of ch...

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Published in:	Molecular genetics & genomic medicine Vol. 12; no. 9; pp. e2478 - n/a
Main Authors:	Yousaf, Ayesha, Yousaf, Sairah, Shabbir, Asra S., Yousaf, Rafia, Riazuddin, Saima, Shaikh, Rehan S., Santos‐Cortez, Regie Lyn P., Ahmed, Zubair M.
Format:	Journal Article
Language:	English
Published:	United States John Wiley & Sons, Inc 01-09-2024 Wiley
Subjects:	Adolescent Adult Amino acids Audiometry Bassoon protein BSN Child Children Chronic Disease chronic suppurative otitis media Comorbidity Consanguinity Ear diseases ear infection Eardrum Ears & hearing Etiology Evolutionary conservation Female Fever Gene sequencing Genes Genetic diversity Genetic variance Genomics Genotype & phenotype Hearing Hearing loss Humans Ionic interactions Male Middle ear missense variants Mutation Mutation, Missense Otitis media Otitis Media, Suppurative - genetics Pakistan Pedigree Protein structure Protein transport Proteins Secondary structure Vertigo Whole genome sequencing Pakistan United States > US Baltimore Maryland ear infection BSN otitis media missense variants chronic suppurative otitis media
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Summary:	Background Otitis media (OM) is the most frequent and complex middle ear condition with multifactorial etiology including genetic predisposition. OM depicts a variable clinical spectrum, leading to speech, developmental delay, and hearing loss. Here, we report the clinical and genetic findings of chronic suppurative otitis media (CSOM) segregating in a six‐generation consanguineous Pakistani family PKOM08. Methods Clinical evaluations, including audio and tympanometry, were conducted to assess OM manifestation and their impact on hearing function. Exome sequencing was performed to identify potential genetic variants underlying CSOM in the study participants. Results Clinical evaluation of participating individuals revealed varying degrees of disease severity, with mild to moderate hearing loss. All the affected individuals had CSOM with no other apparent comorbidity. Whole exome followed by Sanger sequencing revealed two rare heterozygous variants [c.1867C>T, p.(Pro623Ser) and c.11015G>A, p.(Arg3672Gln)] of BSN gene in most of the affected individuals of family PKOM08. BSN encodes a scaffold bassoon protein involved in synaptic vesicle trafficking. The identified variants replaced evolutionary conserved amino acid residues in the encoded protein and are predicted to impact the ionic interactions in the secondary structure. Conclusion A deep intronic variant of BSN has been previously implicated in the etiology of childhood ear infections. Our study further supports a link between BSN‐impaired function and ear infection and CSOM in children. Large consanguineous family segregating chronic suppurative otitis media (CSOM) associated with biallelic variants of BSN. Our study further supports a link between BSN‐impaired function and ear infection and CSOM in children.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ObjectType-Report-3 ObjectType-Case Study-4
ISSN:	2324-9269 2324-9269
DOI:	10.1002/mgg3.2478