Journal article
Variants of LRP2, encoding a multifunctional cell-surface endocytic receptor, associated with hearing loss and retinal dystrophy
Clinical genetics, Vol.103(6), pp.699-703
06/2023
DOI: 10.1111/cge.14312
PMCID: PMC11330644
PMID: 36807241
Abstract
Hereditary deafness and retinal dystrophy are each genetically heterogenous and clinically variable. Three small unrelated families segregating the combination of deafness and retinal dystrophy were studied by exome sequencing (ES). The proband of Family 1 was found to be compound heterozygous for NM_004525.3: LRP2: c.5005A > G, p.(Asn1669Asp) and c.149C > G, p.(Thr50Ser). In Family 2, two sisters were found to be compound heterozygous for LRP2 variants, p.(Tyr3933Cys) and an experimentally confirmed c.7715 + 3A > T consensus splice-altering variant. In Family 3, the proband is compound heterozygous for a consensus donor splice site variant LRP2: c.8452_8452 + 1del and p.(Cys3150Tyr). In mouse cochlea, Lrp2 is expressed abundantly in the stria vascularis marginal cells demonstrated by smFISH, single-cell and single-nucleus RNAseq, suggesting that a deficiency of LRP2 may compromise the endocochlear potential, which is required for hearing. LRP2 variants have been associated with Donnai-Barrow syndrome and other multisystem pleiotropic phenotypes different from the phenotypes of the four cases reported herein. Our data expand the phenotypic spectrum associated with pathogenic variants in LRP2 warranting their consideration in individuals with a combination of hereditary hearing loss and retinal dystrophy.
Details
- Title: Subtitle
- Variants of LRP2, encoding a multifunctional cell-surface endocytic receptor, associated with hearing loss and retinal dystrophy
- Creators
- Rabia Faridi - National Institute on Deafness and Other Communication DisordersRizwan Yousaf - National Institute on Deafness and Other Communication DisordersShoujun Gu - National Institute on Deafness and Other Communication DisordersSayaka Inagaki - National Institute on Deafness and Other Communication DisordersAmy E. Turriff - National Eye InstituteKeith Pelstring - Dayton Children's HospitalBin Guan - National Eye InstituteAmelia Naik - National Eye InstituteAndrew J. Griffith - National Institute on Deafness and Other Communication DisordersSamuel Mawuli Adadey - University of GhanaElvis Twumasi Aboagye - University of GhanaGordon A. Awandare - University of GhanaRobert J. Morell - National Institute on Deafness and Other Communication DisordersEkaterini Tsilou - National Eye InstituteAmanda G. Noyes - GeneDx, Inc, Gaithersburg, Maryland, USA.Laura A. G. Sulmonte - GeneDx, Inc, Gaithersburg, Maryland, USA.Ambroise Wonkam - Johns Hopkins MedicineIsabelle Schrauwen - Columbia University Irving Medical CenterSuzanne M. Leal - Columbia UniversityHela Azaiez - University of IowaCarmen C. Brewer - National Institute on Deafness and Other Communication DisordersSheikh Riazuddin - Allama Iqbal Medical CollegeRobert B. Hufnagel - National Eye InstituteMichael Hoa - National Institute on Deafness and Other Communication DisordersWadih M. Zein - National Eye InstituteJ. Karl de Dios - Dayton Children's HospitalThomas B. Friedman - National Institute on Deafness and Other Communication Disorders
- Resource Type
- Journal article
- Publication Details
- Clinical genetics, Vol.103(6), pp.699-703
- DOI
- 10.1111/cge.14312
- PMID
- 36807241
- PMCID
- PMC11330644
- NLM abbreviation
- Clin Genet
- ISSN
- 0009-9163
- eISSN
- 1399-0004
- Publisher
- Wiley
- Number of pages
- 5
- Grant note
- 107755Z/15/Z; H3A/18/001 / Wellcome Trust U01-HG-009716 / National Human Genome Research Institute; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Human Genome Research Institute (NHGRI) NIDCR Genomics and Computational Biology Core DIR DC000088; DC000039; DC000060; DC000086; R01sDC01165; DC003594; DC016593; DC017712 / NIDCD; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Deafness & Other Communication Disorders (NIDCD) African Academy of Sciences
- Language
- English
- Electronic publication date
- 02/19/2023
- Date published
- 06/2023
- Academic Unit
- Otolaryngology
- Record Identifier
- 9984383902202771
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