Bi-allelic missense variants in human GPN2 result in Perrault syndrome
Perrault syndrome (MIM: 233400, PRLTS1) is a rare autosomal recessive condition characterized by sensorineural hearing loss (SNHL) in both sexes and primary ovarian insufficiency (POI) in 46,XX karyotype females.1 Neurological features, including learning disability, developmental delay, ataxia, and leukodystrophy, also occur in some affected individuals. PRLTS1 is genetically heterogeneous, with bi-allelic variants in 13 genes definitively associated with PRLTS1.2 Most PRLTS1-associated genes encode proteins important for mitochondrial protein translation or peroxisomal function1; nevertheless, many individuals with PRLTS1 remain without a confirmed genetic diagnosis.
Authors
- Alejandro A. Schäffer (ORCID: https://orcid.org/0000-0002-2147-8033)
- Mathilda Wilding (ORCID: https://orcid.org/0000-0001-6054-039X)
- Robert J. Morell (ORCID: https://orcid.org/0000-0003-1537-7356)
- Gavin P. Riordan (ORCID: https://orcid.org/0000-0002-3400-3571)
- Isabelle Schrauwen (ORCID: https://orcid.org/0000-0001-7310-6082)
- Sayaka Inagaki (ORCID: https://orcid.org/0000-0001-9064-0762)
- Bushra Rauf
- Wasim Ahmad (ORCID: https://orcid.org/0000-0003-2639-9200)
- Zubair M. Ahmed (ORCID: https://orcid.org/0000-0003-2914-4502)
- Raymond T. O’Keefe (ORCID: https://orcid.org/0000-0001-8764-1289)
- Amanda McGovern (ORCID: https://orcid.org/0000-0001-7727-3283)
- A. Maqbool (ORCID: https://orcid.org/0009-0003-2867-5042)
- Leigh Demain (ORCID: https://orcid.org/0000-0001-8694-7710)
- Yasuko Ishibashi (ORCID: https://orcid.org/0000-0003-4273-8890)
- Inna A. Belyantseva (ORCID: https://orcid.org/0000-0001-5030-9784)
- Khurram Liaqat (ORCID: https://orcid.org/0000-0002-0792-5773)
- Huw B. Thomas (ORCID: https://orcid.org/0000-0001-9626-9706)
- TB Friedman
- William G. Newman (ORCID: https://orcid.org/0000-0002-6382-4678)
- Muhammad Asad Usmani (ORCID: https://orcid.org/0009-0009-1441-5091)
- Alessandro Rea (ORCID: https://orcid.org/0000-0002-6204-846X)
- R E B Taylor
- Andrew Green (ORCID: https://orcid.org/0000-0002-1077-7417)
- Sheikh Riazuddin (ORCID: https://orcid.org/0000-0002-5671-0437)
- Sondhya Ghedia
- King Lam Lai
- Thomas B. Smith
- Yuliya Sokolova
- Rabia Faridi
- Suzanne M. Leal
- Langping He
- Wade W. Chien
- Saima Riazuddin
- Glenda M. Beaman
- Helen Byers
- Robin Hay
Institutions
- Quaid-i-Azam University (PK)
- University of Maryland, Baltimore (US)
- National Institutes of Health (US)
- University of Arizona (US)
- Allama Iqbal Medical College (PK)
- Columbia University Irving Medical Center (US)
- Royal North Shore Hospital (AU)
- Newcastle upon Tyne Hospitals NHS Foundation Trust (GB)
- University of Manchester (GB)
- Children's Health Ireland at Crumlin (IE)
- St Mary's Hospital (GB)
- Manchester University NHS Foundation Trust (GB)
- Wellcome Centre for Mitochondrial Research (GB)
- National Cancer Institute (US)
- National Institute on Deafness and Other Communication Disorders (US)
- St. Mary's Hospital (GB)
- Newcastle University (GB)
Publication Details
- Journal
- The American Journal of Human Genetics
- Published
- 2026-07-01
- DOI
- https://doi.org/10.1016/j.ajhg.2026.05.016
- Primary Topic
- Mitochondrial Function and Pathology
- Type
- article
- Field-Weighted Citation Impact
- 0.00