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Harboyan syndrome: novel SLC4A11 mutation, clinical manifestations, and outcome of corneal transplantation

Journal of Human Genetics volume 66, pages 193–203 (2021)Cite this article

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Abstract

Harboyan syndrome or corneal dystrophy and progressive deafness (MIM #217400) is characterized by congenital hereditary endothelial dystrophy (CHED) and progressive, sensorineural hearing loss. Mutations in SLC4A11 are responsible for this rare genetic syndrome. Eight patients from seven unrelated families affected with Harboyan Syndrome with mean follow-up of 12.0 ± 0.9 years were thoroughly investigated for the ocular, hearing, and kidney function abnormalities and the outcome of penetrating keratoplasty (PK). Mutation analysis of SLC4A11 was performed. All patients presented with bilateral cloudy corneas since birth. Sensorineural hearing loss was detected in all patients. Seven patients (11 eyes) underwent PK with the median age at surgery of 10.1 years (7.1–22.9). The overall corneal graft survival rate after primary PK was 72.7% (8/11 eyes). The mean graft survival time was 94.6 months (95% CI 83.1–126.0). All patients had unremarkable kidney function. The c.2264G>A (p.Arg755Gln) mutation in SCL4A11 was detected in most patients (87.5%). All unrelated Karen tribe patients had p.Arg755Gln mutation, suggestive of founder effect. We found the allele frequency of this variant in the Karen population to be 0.01. The c.2263C>T (p.Arg755Trp) mutation was found in one patient with mild phenotype and the novel truncating protein mutation c.2127delG (p.Gly710fsx*25) in SCL4A11 was identified in two Thai sisters. Visual outcome and graft survival after PK were satisfactory. Our study shows that all studied patients with SLC4A11 mutations had CHED and sensorineural hearing loss, and SLC4A11 mutations were not related to the onset and severity of hearing loss or outcome of keratoplasty.

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Acknowledgements

We thank our patients and their families for their kind cooperation and for allowing us to use their medical information for the benefit of others. This work was supported by The Thailand Research Fund; and the Faculties of Dentistry and Medicine, Chiang Mai University; and Genomics Thailand Research Grant of Health Systems Research Institute (HSRI) of Thailand.

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Authors and Affiliations

  1. Department of Ophthalmology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand

    Napaporn Tananuvat

  2. Department of Otolaryngology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand

    Rak Tananuvat

  3. Department of Pediatrics, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand

    Wattana Chartapisak

  4. Department of Pathology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand

    Pongsak Mahanupab

  5. Surgery Unit, Nopparat Rajathanee Hospital, Bangkok, Thailand

    Chananya Hokierti

  6. Department of Biochemistry, Faculty of Medical Science, Naresuan University, Phitsanulok, Thailand

    Metawee Srikummool

  7. Department of Biology, Faculty of Science, Chiang Mai University, Chiang Mai, Thailand

    Jatupol Kampuansai

  8. Center of Excellence in Medical Genetics Research, Faculty of Dentistry, Chiang Mai University, Chiang Mai, Thailand

    Worrachet Intachai

  9. Department of Developmental Biology, Harvard School of Dental Medicine, Boston, MA, USA

    Bjorn Olsen

  10. School of Chemistry, Institute of Science, and Center for Biomolecular Structure, Function and Application, Suranaree University of Technology, Nakhon Ratchasima, Thailand

    James R. Ketudat Cairns

  11. Laboratory of Biochemistry, Chulabhorn Research Institute, Bangkok, Thailand

    James R. Ketudat Cairns

  12. Division of Pediatric Dentistry, Department of Orthodontics and Pediatric Dentistry, Faculty of Dentistry, Chiang Mai University, Chiang Mai, Thailand

    Piranit Kantaputra

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Correspondence to Piranit Kantaputra.

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All procedures were reviewed and approved by the Research and Ethics Committee, Faculty of Medicine, Chiang Mai University (Study Code: OPT-2561-06011) and followed the tenets of the Declaration of Helsinki. Informed consent was obtained from the patients or their parents.

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Tananuvat, N., Tananuvat, R., Chartapisak, W. et al. Harboyan syndrome: novel SLC4A11 mutation, clinical manifestations, and outcome of corneal transplantation. J Hum Genet 66, 193–203 (2021). https://doi.org/10.1038/s10038-020-00834-5

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