Evidence map›Paper›PMID 40549196›Full record

ArticleMolecular genetics and genomics : MGG2025

Enhanced identification of novel pathogenic variants in hereditary hearing loss through physical phasing with integrated short and long-read sequencing data.

Lu Kang, Qian Zhang, Chao Wang, Jia Geng, Xinlei Li, Mingjun Zhong, Sihan Liu, Xuegang Wang, Yu Lu, Jing Cheng and 3 more

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In one paragraph

Article in Molecular genetics and genomics : MGG, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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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3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

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

13 authors.

Lu KangDepartment of Otolaryngology- Head & Neck Surgery, Institute of Rare Diseases, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Qian ZhangDepartment of Otolaryngology- Head & Neck Surgery, Institute of Rare Diseases, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Chao WangDepartment of Otolaryngology- Head & Neck Surgery, Institute of Rare Diseases, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Jia GengDepartment of Otolaryngology- Head & Neck Surgery, Institute of Rare Diseases, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Xinlei LiMedical Center of Hematology, Xinqiao Hospital, Army Medical University, Chongqing, China.
Mingjun ZhongDepartment of Otolaryngology- Head & Neck Surgery, Institute of Rare Diseases, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Sihan LiuDepartment of Otolaryngology- Head & Neck Surgery, Institute of Rare Diseases, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Xuegang WangDepartment of Otolaryngology- Head & Neck Surgery, Institute of Rare Diseases, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Yu LuDepartment of Otolaryngology- Head & Neck Surgery, Institute of Rare Diseases, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Jing ChengDepartment of Otolaryngology- Head & Neck Surgery, Institute of Rare Diseases, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Yongxin MaDepartment of Medical Genetics, West China Hospital, Sichuan University, Chengdu, China.
Fengxiao BuDepartment of Otolaryngology- Head & Neck Surgery, Institute of Rare Diseases, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, China. bufengxiao@wchscu.cn.ORCID http://orcid.org/0000-0002-4882-4856
Huijun YuanDepartment of Otolaryngology- Head & Neck Surgery, Institute of Rare Diseases, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, China. yuanhj301@wchscu.cn.

Funding

1•3•5 project for disciplines of excellence, West China Hospital, Sichuan University ZYJC20002National Natural Science Foundation of China 82171836
6 · The paper itself

Abstract

Haplotagged variant calling is essential for determining genetic etiologies in hereditary hearing loss (HHL) cases when familial testing is unavailable, and long-read whole-genome sequencing (lrWGS) enables this by outperforming in several key areas: enhanced detection of structural variations (SVs) and precise long-range haplotype phasing. In this study, we enrolled two HL cases from the China Deafness Genetics Consortium (CDGC) cohort, whose genetic tests were previously inconclusive due to a lack of pedigree segregation data. Small variants (including SNVs and InDels) profiles were generated by short-read whole-genome sequencing (srWGS), while SVs were identified and co-phased with small variants using a read-based approach. As a result, 87% and 83% of the chromosomal regions were successfully phased, and reached mean haplotype block lengths up to 661.9 kb and 309.9 kb, respectively. A total of 483 and 434 small variants, along with three and six heterozygous SVs in coding and splice regions of 201 HL-associated genes were phased. Pathogenic interpretations resolved compound heterozygosity in MARVELD2, identifying a pathogenic (P) variant NM_001038603.3:c.782G > A in trans with a novel pathogenic (P) deletion (NM_001038603.3:c.1183-1288_1503 + 195del). Additionally, we identified a known P variant NM_022124.6:c.5369-1G > A, which was oriented in trans with a P deletion NM_022124.6:c.-5-12_67 + 154del in the CDH23 gene. This study demonstrates the clinical utility of integrating srWGS and Nanopore lrWGS for comprehensive variant detection and haplotype determination in HL cases with limited family background details, providing a robust framework for resolving complex genetic etiologies and improving diagnostic precision.

Indexed as

Hearing LossChinaFemaleHaplotypesHigh-Throughput Nucleotide SequencingHumansMalePedigreeWhole Genome SequencingCDH23Haplotype phasingHearing lossLong-readMARVELD2Structural variation

Identifiers

PMID40549196

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Registered trials

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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.