Kiaa1024L/Minar2 is essential for hearing by regulating cholesterol distribution in hair bundles

Gao, Ge; Guo, Shuyu; Zhang, Quan; Zhang, Hefei; Zhang, Cuizhen; Peng, Gang

doi:10.7554/elife.80865

Cited by 5 publications

(4 citation statements)

References 124 publications

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“…Electrodes were insulated stainless steel, and the recording conditions were the same as those described in prior work. 115 LFP signals were sampled at 5 kHz, denoised via wavelet decomposition, and any epileptiform discharges were identified and quantified using custom MATLAB scripts (https://github.com/gpeng1903/danioLFP).…”

Section: Methodsmentioning

confidence: 99%

Exome Sequencing of 963 Chinese Families Identifies Novel Epilepsy Candidate Genes

Ma,

Su,

Zhou

et al. 2024

Preprint

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Epilepsy, a prevalent neurodevelopmental disorder in children, is often accompanied by detrimental psychological consequences and other comorbidities. We performed exome sequencing on 963 patient-parent trios, revealing differences in genetic epidemiology between Chinese and European epilepsy cohorts. The diagnostic yield for known epilepsy genes was 40%. Pathogenic variants were most commonly found in SCN1A, KCNQ2, and DEPDC5. Additionally, we identified 15 novel monogenic epilepsy candidates in at least two patients diagnosed with developmental and epileptic encephalopathy, non-acquired focal epilepsy, or genetic generalized epilepsy, includingADCY2, BCAR3, CDC45, CHRNG, CRTC2, CSMD1, CSMD2, KDM6B, KIF1B, PLEKHM3, PPP4R1, RASGRP2, SGSM2, SYNE1, andZFHX3. Aside fromADCY2, which was implicated in the GABAergic synapse pathway based on KEGG analysis, these candidates do not belong to known epilepsy pathways. Local field potential recordings in zebrafish and calcium imaging experiments validated associations for 11 of these genes, excluding those unsuitable for functional analyses. Furthermore, we found thatCRTC2overexpression leads to hippocampal neuronal hyperactivity using multi-electrode arrays and electrophysiology. We have documented the first-line medications prescribed for patients harboring variants in the novel candidate genes. This study expands our understanding of the genetic underpinnings of epilepsy and provides opportunities for early diagnosis and personalized medicine approaches.

show abstract

Section: Methodsmentioning

confidence: 99%

Exome Sequencing of 963 Chinese Families Identifies Novel Epilepsy Candidate Genes

Ma,

Su,

Zhou

et al. 2024

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…1B). Furthermore, patients with DEE were diagnosed with infantile epileptic spasms syndrome (IESS) (113,11.7%), Dravet syndrome (DS) (21, 2.2%), Lennox-Gastaut syndrome (LGS) (15, 1.6%), DEE with spike-and-wave activation in sleep (DEE-SWAS) (18, 1.9%), and Etiology-speci c DEEs (140, 14.5%) (Fig. 1B).…”

Section: Demographics and Clinical Datamentioning

confidence: 99%

“…Electrodes were insulated stainless steel, and the recording conditions were the same as those described in prior work. 113 LFP signals were sampled at 5 kHz, denoised via wavelet decomposition, and any epileptiform discharges were identi ed and quanti ed using custom MATLAB scripts (https://github.com/gpeng1903/danioLFP).…”

Section: Local Eld Potential (Lfp) Recordingmentioning

confidence: 99%

Exome Sequencing of 963 Chinese Families Identifies Novel Epilepsy Candidate Genes

Fan,

Ma,

et al. 2024

Preprint

View full text Add to dashboard Cite

Epilepsy, a prevalent neurodevelopmental disorder in children, is often accompanied by detrimental psychological consequences and other comorbidities. We perform exome sequencing on 963 patient-parent trios, revealing differences in genetic epidemiology between Chinese and European epilepsy cohorts. The diagnostic yield for known epilepsy genes is 40%. Pathogenic variants are most commonly identified in SCN1A, KCNQ2, and DEPDC5. Additionally, we identify 15 novel monogenic epilepsy candidates in at least two patients diagnosed with developmental and epileptic encephalopathy, non-acquired focal epilepsy, or genetic generalized epilepsy, including ADCY2, BCAR3, CDC45, CHRNG, CRTC2, CSMD1, CSMD2, KDM6B, KIF1B, PLEKHM3, PPP4R1, RASGRP2, SGSM2, SYNE1, and ZFHX3. Aside from ADCY2, which is implicated in the GABAergic synapse pathway based on KEGG analysis, the remaining 14 candidates do not belong to known epilepsy pathways. Local field potential recordings in zebrafish and calcium imaging experiments validated associations for 11 candidates, excluding those unsuitable for functional analyses. Furthermore, CRTC2 overexpression leads to hippocampal neuronal hyperactivity using multi-electrode arrays and electrophysiology. We have documented the first-line medications prescribed for patients harboring variants in the novel candidate genes. This study expands our understanding of the genetic underpinnings of epilepsy and provides opportunities for early diagnosis and personalized medicine approaches.

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“…Fixed larvae were permeabilized in 1% Triton X-100/1 Â PBS for 1 h at room temperature. After blocked and washed, samples were incubated with primary antibodies and then with secondary antibodies (Gao et al, 2022).…”

Section: Immunofluorescent Stainingmentioning

confidence: 99%

Ap4s1 truncation leads to axonal defects in a zebrafish model of spastic paraplegia 52

Li,

Zhang,

Peng

2023

Intl J of Devlp Neuroscience

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Biallelic mutations in AP4S1, the σ4 subunit of the adaptor protein complex 4 (AP‐4), lead to autosomal recessive spastic paraplegia 52 (SPG52). It is a subtype of AP‐4‐associated hereditary spastic paraplegia (AP‐4‐HSP), a complex childhood‐onset neurogenetic disease characterized by progressive spastic paraplegia of the lower limbs. This disease has so far lacked effective treatment, in part due to a lack of suitable animal models. Here, we used CRISPR/Cas9 technology to generate a truncation mutation in the ap4s1 gene in zebrafish. The ap4s1 truncation led to motor impairment, delayed neurodevelopment, and distal axonal degeneration. This animal model is useful for further research into AP‐4 and AP‐4‐HSP.

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Kiaa1024L/Minar2 is essential for hearing by regulating cholesterol distribution in hair bundles

Cited by 5 publications

References 124 publications

Exome Sequencing of 963 Chinese Families Identifies Novel Epilepsy Candidate Genes

Exome Sequencing of 963 Chinese Families Identifies Novel Epilepsy Candidate Genes

Exome Sequencing of 963 Chinese Families Identifies Novel Epilepsy Candidate Genes

Ap4s1 truncation leads to axonal defects in a zebrafish model of spastic paraplegia 52

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