Purpose: The aim of this study was to determine the genetic cause of autosomal dominant nonsyndromic hearing loss segregating in a multigenerational family.
Methods: Clinical examination, genome-wide linkage analysis, and exome sequencing were carried out on the family.
Results: Affected individuals presented with early-onset progressive mild hearing impairment with a fairly flat, gently downsloping or U-shaped audiogram configuration. Detailed clinical examination excluded any additional symptoms. Linkage analysis detected an interval on chromosome 1p21 with a logarithm of the odds (LOD) score of 8.29: designated locus DFNA37. Exome sequencing identified a novel canonical acceptor splice-site variant c.652-2A>C in the COL11A1 gene within the DFNA37 locus. Genotyping of all 48 family members confirmed segregation of this variant with the deafness phenotype in the extended family. The c.652-2A>C variant is novel, highly conserved, and confirmed in vitro to alter RNA splicing.
Conclusion: We have identified COL11A1 as the gene responsible for deafness at the DFNA37 locus. Previously, COL11A1 was solely associated with Marshall and Stickler syndromes. This study expands its phenotypic spectrum to include nonsyndromic deafness. The implications of this discovery are valuable in the clinical diagnosis, prognosis, and treatment of patients with COL11A1 pathogenic variants.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6431578 | PMC |
| http://dx.doi.org/10.1038/s41436-018-0285-0 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Next-Generation Sequencing of Chinese Children with Congenital Hearing Loss Reveals Rare and Novel Variants in Known and Candidate Genes.
Biomedicines
November 2024
Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Hearing loss (HL) is the most common disorder in newborns with a highly heterogeneous genetic background. Despite significant progress in screening and identifying genes related to congenital hearing loss, there are still candidate genes implicated in HL that remain undiscovered. We investigated HL in 43 Chinese families by segregating bilateral sensorineural HL via whole-exome sequencing (WES) and Sanger sequencing.
View Article and Find Full Text PDFPatients with a Wide Range of Disorders Related to Gene Variants: Novel Mutations and Genotype-Phenotype Correlations.
Genes (Basel)
December 2024
Department of Clinical Genetics, Medical University of Lodz, Pomorska Str. 251, 92-213 Lodz, Poland.
-spectrum disorders are caused by a mutation in the gene. The term includes a wide range of rare disorders, from the most severe Wolfram syndrome with autosomal recessive inheritance to milder clinical manifestations with a single causative variant in the gene, such as Wolfram-like syndrome, low-frequency sensorineural hearing loss (LFSNHL), isolated diabetes mellitus (DM), nonsyndromic optic atrophy (OA), and isolated congenital cataracts. The aim of this study was to evaluate genotype-phenotype correlations in Polish patients with -spectrum disorders.
View Article and Find Full Text PDFPhosphoribosyl pyrophosphate synthetase 1 () associated retinal degeneration: an international study.
Ophthalmic Genet
January 2025
Department of Ophthalmology, Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, USA.
Introduction: Phosphoribosyl pyrophosphate synthetase 1 () is an X-linked gene critical for nucleotide metabolism. Pathogenic variants cause three overlapping phenotypes: Arts syndrome (severe neurological disease), Charcot-Marie-Tooth type 5 [CMTX5] (peripheral neuropathy), and non-syndromic sensorineural hearing loss (SNHL). Each may be associated with retinal dystrophy.
View Article and Find Full Text PDFA Novel Homozygous Loss-of-Function Variant in GPR156 Delineates Non-syndromic Hearing Loss.
Biochem Genet
January 2025
Department of Dermatology, Yale University School of Medicine, New Haven, CT, USA.
Non-syndromic hearing loss (NSHL) is a genetically heterogeneous disorder accounting for almost 70% of the total congenital hearing loss. The implementation of rapid advanced sequencing methods has significantly contributed to the correct molecular diagnosis for several rare genetic disorders, including NHSL. Features of two probands with NHSL were clinically and genetically evaluated.
View Article and Find Full Text PDFGenetic landscape in undiagnosed patients with syndromic hearing loss revealed by whole exome sequencing and phenotype similarity search.
Hum Genet
January 2025
Division of Hearing and Balance Research, National Institute of Sensory Organs, NHO Tokyo Medical Center, 2-5-1 Higashigaoka, Meguro-Ku, Tokyo, 152-8902, Japan.
There are hundreds of rare syndromic diseases involving hearing loss, many of which are not targeted for clinical genetic testing. We systematically explored the genetic causes of undiagnosed syndromic hearing loss using a combination of whole exome sequencing (WES) and a phenotype similarity search system called PubCaseFinder. Fifty-five families with syndromic hearing loss of unknown cause were analyzed using WES after prescreening of several deafness genes depending on patient clinical features.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!