Background: Perrault syndrome is an inherited disorder with clinical findings that differ according to sex. It is characterized by a variable age of onset and sensorineural hearing loss in both sexes, as well as ovarian dysfunction in females with a 46,XX karyotype. Although it is a rare autosomal recessive syndrome, with approximately 100 affected individuals reported in the literature, it shows both genotypic and phenotypic variations. Mutations in the HSD17B4 gene have been identified as one of the genetic causes of Perrault syndrome. Case Presentation: A female case and a male case from two different unrelated families with a new variant in the HSD17B4 gene, which were not previously described in the literature and were accompanied by hearing loss, skeletal anomalies, and neurological symptoms, were presented. Conclusion: We defined Perrault syndrome cases in Turkey caused by a novel mutation in HSD17B4. Whole-exome sequencing is a useful diagnostic technique with varying clinical results due to genetic and phenotypic heterogeneity.

1.
Adzhubei IA, Schmidt S, Peshkin L, Ramensky VE, Gerasimova A, Bork P, et al. A method and server for predicting damaging missense mutations. Nat Methods. 2010;7(4):248–9.
2.
Demain LA, Urquhart JE, O'Sullivan J, Williams SG, Bhaskar SS, Jenkinson EM, et al. Expanding the genotypic spectrum of Perrault syndrome. Clin Genet. 2017;91(2):302–12.
3.
Faridi R, Rea A, Fenollar-Ferrer C, O’Keefe RT, Gu S, Munir Z, et al. New insights into Perrault syndrome, a clinically and genetically heterogeneous disorder. Hum Genet. 2022;141(3–4):805–19.
4.
Fiumara A, Sorge G, Toscano A, Parano E, Pavone L, Opitz JM. Perrault syndrome: evidence for progressive nervous system involvement. Am J Med Genet. 2004;128A(3):246–9.
5.
Jenkinson EM, Rehman AU, Walsh T, Clayton-Smith J, Lee K, Morell RJ, et al. Perrault syndrome is caused by recessive mutations in CLPP, encoding a mitochondrial ATP-dependent chambered protease. Am J Hum Genet. 2013;92(4):605–13.
6.
Lerat J, Jonard L, Loundon N, Christin-Maitre S, Lacombe D, Goizet C, et al. An application of NGS for molecular investigations in Perrault syndrome: study of 14 families and review of the literature. Hum Mutat. 2016;37(12):1354–62.
7.
Lieber DS, Calvo SE, Shanahan K, Slate NG, Liu S, Hershman SG, et al. Targeted exome sequencing of suspected mitochondrial disorders. Neurology. 2013;80(19):1762–70.
8.
Lieber DS, Hershman SG, Slate NG, Calvo SE, Sims KB, Schmahmann JD, et al. Next generation sequencing with copy number variant detection expands the phenotypic spectrum of HSD17B4-deficiency. BMC Med Genet. 2014;15:30.
9.
McMillan HJ, Worthylake T, Schwartzentruber J, Gottlieb CC, Lawrence SE, Mackenzie A, et al. Specific combination of compound heterozygous mutations in 17β-hydroxysteroid dehydrogenase type 4 (HSD17B4) defines a new subtype of D-bifunctional protein deficiency. Orphanet J Rare Dis. 2012;7:90.
10.
Nishi Y, Hamamoto K, Kajiyama M, Kawamura I. The Perrault syndrome: clinical report and review. Am J Med Genet. 1988;31(3):623–9.
11.
Pan Z, Xu H, Tian Y, Liu D, Liu H, Li R, et al. Perrault syndrome: clinical report and retrospective analysis. Mol Genet Genomic Med. 2020;8(10):e1445.
12.
Pierce SB, Walsh T, Chisholm KM, Lee MK, Thornton AM, Fiumara A, et al. Mutations in the DBP-deficiency protein HSD17B4 cause ovarian dysgenesis, hearing loss, and ataxia of Perrault Syndrome. Am J Hum Genet. 2010;87(2):282–8.
13.
Roberts LM, Carnivale B. Perrault syndrome diagnosis in a patient presenting to her primary care provider with secondary amenorrhea. Case Rep Obstet Gynecol. 2019;2019:9865281.
14.
Schwarz JM, Cooper DN, Schuelke M, Seelow D. MutationTaster2: mutation prediction for the deep-sequencing age. Nat Methods. 2014;11(4):361–2.
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