LHFPL5 mutation: A rare cause of non-syndromic autosomal recessive hearing loss

Al-Amri, Ahmed; Saegh, Abeer Al; Al-Mamari, Watfa; El‐Asrag, Mohammed E.; Al-Kindi, Mohammed Nasser; Khabouri, Mazin Al; Al-Wardy, Nadia; Lamki, Khalsa Al; Gabr, Ahlam; Idris, Ahmed; Inglehearn, Chris F.; Clapcote, Steven J.; Ali, Manir

doi:10.1016/j.ejmg.2018.11.026

Cited by 7 publications

(2 citation statements)

References 14 publications

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“…LHFPL5 encodes LHFPL tetraspan subfamily member 5, a member of the lipoma HMGIC fusion partner (LHFP) family, a subset of the superfamily of tetraspan transmembrane proteins. Mutations in this gene result in deafness, and it is proposed to function in the inner ear as a component of the hair cell's mechanotransduction machinery ( 49 ). The SNV causing the G4-Var identified here (Table 1 and Supplementary Figure S3F ) is associated with deafness ( 50 ) ( https://www.ncbi.nlm.nih.gov/clinvar/RCV000288173/ ), although there is no reported association of this variant with changes in transcriptional expression.…”

Section: Resultsmentioning

confidence: 99%

Genetic variations in G-quadruplex forming sequences affect the transcription of human disease-related genes

Lorenzatti,

Piga,

Gismondi

et al. 2023

Nucleic Acids Research

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Guanine-rich DNA strands can fold into non-canonical four-stranded secondary structures named G-quadruplexes (G4s). G4s folded in proximal promoter regions (PPR) are associated either with positive or negative transcriptional regulation. Given that single nucleotide variants (SNVs) affecting G4 folding (G4-Vars) may alter gene transcription, and that SNVs are associated with the human diseases’ onset, we undertook a novel comprehensive study of the G4-Vars genome-wide (G4-variome) to find disease-associated G4-Vars located into PPRs. We developed a bioinformatics strategy to find disease-related SNVs located into PPRs simultaneously overlapping with putative G4-forming sequences (PQSs). We studied five G4-Vars disturbing in vitro the folding and stability of the G4s located into PPRs, which had been formerly associated with sporadic Alzheimer's disease (GRIN2B), a severe familiar coagulopathy (F7), atopic dermatitis (CSF2), myocardial infarction (SIRT1) and deafness (LHFPL5). Results obtained in cultured cells for these five G4-Vars suggest that the changes in the G4s affect the transcription, potentially contributing to the development of the mentioned diseases. Collectively, data reinforce the general idea that G4-Vars may impact on the different susceptibilities to human genetic diseases’ onset, and could be novel targets for diagnosis and drug design in precision medicine.

show abstract

Section: Resultsmentioning

confidence: 99%

Genetic variations in G-quadruplex forming sequences affect the transcription of human disease-related genes

Lorenzatti,

Piga,

Gismondi

et al. 2023

Nucleic Acids Research

View full text Add to dashboard Cite

show abstract

“…LHFPL5 encodes LHFPL tetraspan subfamily member 5, a member of the lipoma HMGIC fusion partner (LHFP) family, a subset of the superfamily of tetraspan transmembrane proteins. Mutations in this gene result in deafness, and it is proposed to function in the inner ear as a component of the hair cell’s mechanotransduction machinery (44). The SNV causing the G4-Var identified here (Table 1 and Supplementary Figure S3F) is associated with deafness (45).…”

Section: Resultsmentioning

confidence: 99%

Genetic variations in G-Quadruplex forming sequences affect the transcription of human disease-related genes

Lorenzatti

Piga

Gismondi

et al. 2022

Preprint

View full text Add to dashboard Cite

Guanine-rich DNA strands can fold into non-canonical four-stranded secondary structures named G-quadruplexes (G4s). G4s folded in proximal promoter regions (PPR) are associated either with positive or negative transcriptional regulation. Given that single nucleotide variants (SNVs) affecting G4 folding (G4-Vars) may alter gene transcription, and that SNVs are associated with the human diseases' onset, we undertook a comprehensive study of the G4-Vars genome-wide (G4-variome) to find disease-associated G4-Vars located into PPRs. We developed a bioinformatics strategy to find disease-related SNVs located into PPRs simultaneously overlapping with putative G4-forming sequences (PQSs). We studied five G4-Vars disturbing in vitro the folding and stability of the G4s located into PPRs, which had been formerly associated with sporadic Alzheimer's disease (GRIN2B), a severe familiar coagulopathy (F7), atopic dermatitis (CSF2), myocardial infarction (SIRT1), and deafness (LHFPL5). Results obtained in cellulo for GRIN2B and F7 suggest that the G4 disruption due to the identified G4-Vars affect the transcription and are responsible for the mentioned diseases. Collectively, data suggest that G4-Vars may account for the different susceptibilities to human genetic diseases' onset, and could be novel targets for diagnosis and drug design in precision medicine.

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Genetic etiology of hereditary hearing loss in the Gulf Cooperation Council countries

et al. 2021

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LHFPL5 mutation: A rare cause of non-syndromic autosomal recessive hearing loss

Cited by 7 publications

References 14 publications

Genetic variations in G-quadruplex forming sequences affect the transcription of human disease-related genes

Genetic variations in G-quadruplex forming sequences affect the transcription of human disease-related genes

Genetic variations in G-Quadruplex forming sequences affect the transcription of human disease-related genes

Genetic etiology of hereditary hearing loss in the Gulf Cooperation Council countries

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