Evidence map›Paper›PMID 42322530›Full record

ArticleBiochemical genetics2026

A Splice-Site Variant in ACY1 Associated with Congenital Hearing Loss: Clinical, Biochemical, and Zebrafish Functional Evidence.

Sha Yu, Zhenmin Xu, Huijun Wang, Liheng Chen, Shao Wei Hu, Yunfei Zhang, Huiying Lyu, Hongjiang Wu, Mengyuan Wu, Yilai Shu and 1 more

Abstract read
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In one paragraph

Article in Biochemical genetics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

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0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

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PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Sha YuENT Institute and Department of Otorhinolaryngology, Eye & ENT Hospital, Fudan University, 83 Fen Yang Road, Shanghai, 200031, China.
Zhenmin XuDepartment of Otolaryngology-Head and Neck Surgery, Children's Hospital of Fudan University, 399 Wan Yuan Road, Shanghai, 201102, China.
Huijun WangCenter for Molecular Medicine, Pediatrics Research Institute, Children's Hospital of Fudan University, Shanghai, 201102, China.
Liheng ChenENT Institute and Department of Otorhinolaryngology, Eye & ENT Hospital, Fudan University, 83 Fen Yang Road, Shanghai, 200031, China.
Shao Wei HuENT Institute and Department of Otorhinolaryngology, Eye & ENT Hospital, Fudan University, 83 Fen Yang Road, Shanghai, 200031, China.
Yunfei ZhangDepartment of Otolaryngology-Head and Neck Surgery, Children's Hospital of Fudan University, 399 Wan Yuan Road, Shanghai, 201102, China.
Huiying LyuDepartment of Otolaryngology-Head and Neck Surgery, Children's Hospital of Fudan University, 399 Wan Yuan Road, Shanghai, 201102, China.
Hongjiang WuCenter for Molecular Medicine, Pediatrics Research Institute, Children's Hospital of Fudan University, Shanghai, 201102, China.
Mengyuan WuCenter for Molecular Medicine, Pediatrics Research Institute, Children's Hospital of Fudan University, Shanghai, 201102, China.
Yilai ShuENT Institute and Department of Otorhinolaryngology, Eye & ENT Hospital, Fudan University, 83 Fen Yang Road, Shanghai, 200031, China. yilai_shu@fudan.edu.cn.
Wenxia ChenDepartment of Otolaryngology-Head and Neck Surgery, Children's Hospital of Fudan University, 399 Wan Yuan Road, Shanghai, 201102, China. george501@sina.com.

Funding

National Natural Science Foundation of China 82225014Science and Technology Commission of Fengxian District, Shanghai Municipality 18411965500Science and Technology Innovation Program of Hunan Province 2023RC4005
6 · The paper itself

Abstract

Variants in the aminoacylase 1 (ACY1) gene are associated with diverse clinical phenotypes, but their roles in hearing loss remain unclear. This study aimed to investigate the potential role of ACY1 in hearing loss. Exome sequencing was performed on 396 patients with sensorineural hearing loss. We identified a homozygous splicing variant, c.1063-1G>A, in ACY1 as a plausible candidate variant in a 5-year-old girl with congenital hearing loss and normal developmental milestones over a 4-year follow-up. Functional assays, including urinary organic acid analysis and aminoacylase 1 enzyme activity testing in Epstein-Barr virus (EBV)-transformed lymphoblasts, confirmed aminoacylase 1 deficiency in the patient. In vitro splicing assays showed that the c.1063-1G>A variant activated a cryptic splice site, causing aberrant splicing, a frameshift, and a premature stop codon. A zebrafish model with morpholino-mediated acy1 knockdown revealed a significant reduction in hair cells and impaired auditory function, which were effectively rescued by wild-type but not mutant human ACY1 mRNA. Furthermore, transcriptomic profiling of zebrafish auditory hair cells, combining fluorescence-activated cell sorting (FACS) with RNA sequencing, revealed downregulation of critical inner ear development genes, including gfi1ab and atoh1a/b, which was validated by RT-qPCR. These results provide clinical and experimental evidence supporting the functional impact of the ACY1 c.1063-1G>A variant and its potential involvement in congenital hearing loss. Our findings support ACY1 as a candidate gene for hereditary hearing impairment, although additional unrelated patients and independent validation are needed to further establish the gene-disease relationship.

Indexed as

ACY1EBV-transformed lymphoblastsExome sequencingHearing lossTranscriptome analysisZebrafish

Identifiers

PMID42322530

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.