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Perrault Syndrome Type 1 via the HSD17B4 Gene

Summary and Pricing

Test Method

Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture Probes
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
HSD17B4 81479 81479,81479 $990
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
4645HSD17B481479 81479,81479 $990 Order Options and Pricing

Pricing Comments

Testing run on PG-select capture probes includes CNV analysis for the gene(s) on the panel but does not permit the optional add on of exome-wide CNV analysis. Any of the NGS platforms allow reflex to other clinically relevant genes, up to whole exome or whole genome sequencing depending upon the base platform selected for the initial test.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

This test is also offered via a custom panel (click here) on our exome or genome backbone which permits the optional add on of exome-wide CNV or genome-wide SV analysis.

Turnaround Time

3 weeks on average for standard orders or 2 weeks on average for STAT orders.

Please note: Once the testing process begins, an Estimated Report Date (ERD) range will be displayed in the portal. This is the most accurate prediction of when your report will be complete and may differ from the average TAT published on our website. About 85% of our tests will be reported within or before the ERD range. We will notify you of significant delays or holds which will impact the ERD. Learn more about turnaround times here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.


Genetic Counselors


  • Ben Dorshorst, PhD

Clinical Features and Genetics

Clinical Features

Perrault syndrome is a sex-influenced disorder that is characterized by progressive, sensorineural deafness coupled with ovarian dysgenesis or premature ovarian failure (streak gonads) and infertility in females. This syndrome often goes undetected until puberty or during child-bearing age (Pierce et al. 2010). Perrault syndrome also affects males and is mainly characterized by progressive hearing loss; however, it is often underdiagnosed because hypogonadism is not always observed in male patients. Some patients diagnosed with Perrault syndrome also develop neurologic abnormalities, which include mild mental retardation, cerebellar ataxia, and disruptions involving the peripheral nervous system (Huyghe et al. 2006). Due to the clinical heterogeneity of this deafness syndrome, Perrault syndrome has been further classified into two types. Type 1 is described as static and does not present with neurologic disease, whereas type II is characterized by progressive neurologic disease.

Diagnosing Perrault syndrome in a male patient can be very challenging, especially in the absence of a sister that presents specific symptoms of the syndrome. The average age at diagnosis of Perrault syndrome in females is 22 years old, which is often ascertained by a delay in puberty and the development of sensorineural deafness. Hearing loss in Perrault syndrome is always bilateral, although the severity can be variable (ranging from mild to profound deafness). Ovarian dysgenesis occurs in all female Perrault syndrome patients and is often validated by amenorrhea; however, males do not show any gonadal defects. Approximately 50% of patients with Perrault syndrome show delayed growth, with height often below the third percentile. Male patients with Perrault syndrome could present with cerebellar ataxia combined with peripheral neuropathy, as well as azoospermia (Lieber et al. 2014).


Perrault syndrome follows an autosomal recessive pattern of inheritance and is caused by variants in the HSD17B4 gene, also known as PRLTS1, which has been localized to chromosomal band 5q23.1. The HSD17B4 gene encodes an enzyme called 17-beta-estradiol dehydrogenase, also known as D-bifunctional protein (D-BP), multifunctional enzyme type 2 (MFE-2), and multifunctional protein-2 (MFP-2), which is involved in the beta-oxidation of fatty acids in peroxisomes (Ferdinandusse et al. 2006; Huyghe et al. 2006; Mehtala et al. 2013). The HSD17B4 gene consists of 24 exons and covers approximately 100 kb. Other genes implicated in the development of Perrault syndrome include CLPP (PRLTS3), HARS2 (PRLTS2), and LARS2 (PRLTS4).

The enzyme 17-beta-estradiol dehydrogenase is mainly found in the liver, kidney, ovaries, and testes (De Launoit and Adamski 1999; Huyghe et al. 2006). The HSD17B4 gene is generally stimulated by progesterone, as well as ligands of the peroxisomal proliferator-activated receptor alpha (PPARalpha), including clofibrate. Phorbol esters inhibit the expression of this gene. Mutations in the HSD17B4 gene are also known to cause Zellweger syndrome and peroxisomal D-bifunctional protein deficiency, which also present with hearing impairment (De Launoit and Adamski 1999; Lines et al. 2014).

Most cases of Perrault syndrome are simultaneously reported in at least two female members of a family. In cases where two brothers are involved, these individuals often present a relatively mild phenotype, possibly because only one of the two major domains of the enzyme is affected (either the dehydrogenase or the hydratase domain). A total of about 80 causative mutations in the HSD17B4 gene have been reported, which include missense mutations, deletions, insertions, and duplications (Pierce et al. 2010).

Recessive mutations in the HSD17B4 gene also cause D-BP deficiency. D-BP deficiency is commonly fatal in early childhood, a small number of patients survive beyond 8 years of age (Van Grunsven et al. 1999; McMillan et al. 2012).

Clinical Sensitivity - Sequencing with CNV PG-Select

Variants in the HSD17B4 gene have been reported in three out of 6 families with Perrault syndrome (Pierce et al. 2010; Pierce et al. 2011; Pierce et al. 2013; MacMillan et al. 2012; Lines et al. 2014). The analytical sensitivity of bi-directional sequencing is also high because all HSD17B4 causative mutations reported to date are detectable by this method.

In a study involving 110 patients with D-BP deficiency, only two patients were determined to have gross deletions, whereas the majority of the detected variants were missense mutations (Ferdinandusse et al. 2006).

Testing Strategy

This test provides full coverage of all coding exons of the HSD17B4 gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.

Indications for Test

Individuals with bilateral sensorineural hearing loss with early-childhood onset can be offered the HSD17B4 test. There should also be no evidence of impaired vestibular function, as indicated by computed tomography (CT) imaging (Kumar et al. 2003; Altay et al. 2008). Audioprofiling may also assist in determining the rate of progressive hearing loss each year. Cascade testing or successive testing of family members to trace the inheritance pattern of the identified mutation may be offered when the patient has been identified as the index case or proband. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in HSD17B4.


Official Gene Symbol OMIM ID
HSD17B4 601860
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


Name Inheritance OMIM ID
Perrault Syndrome AR 233400

Related Tests

Perrault Syndrome Type 2 via the HARS2 Gene
Perrault Syndrome Type 3 and Deafness, Autosomal Recessive 8 (DFNB8) via the CLPP Gene
Perrault Syndrome Type 4 via the LARS2 Gene


  • Altay H, Savas R, Ogüt F, Kirazli T, Alper H. 2008. CT and MRI findings in X-linked progressive deafness.  Diagn Interv Radiol 14: 117–119. PubMed ID: 18814129
  • de Launoit Y de, Adamski J. 1999. Unique multifunctional HSD17B4 gene product: 17beta-hydroxysteroid dehydrogenase 4 and D-3-hydroxyacyl-coenzyme A dehydrogenase/hydratase involved in Zellweger syndrome. J. Mol. Endocrinol. 22: 227–240. PubMed ID: 10343282
  • Ferdinandusse S, Ylianttila MS, Gloerich J, Koski MK, Oostheim W, Waterham HR, Hiltunen JK, Wanders RJ, Glumoff T. 2006. Mutational spectrum of D-bifunctional protein deficiency and structure-based genotype-phenotype analysis. The American Journal of Human Genetics 78: 112–124. PubMed ID: 16385454
  • Huyghe S, Schmalbruch H, Hulshagen L, Veldhoven PV, Baes M, Hartmann D. 2006. Peroxisomal Multifunctional Protein-2 Deficiency Causes Motor Deficits and Glial Lesions in the Adult Central Nervous System. The American Journal of Pathology 168: 1321–1334. PubMed ID: 16565505
  • Kumar G, Castillo M, Buchman CA. 2003. X-linked stapes gusher: CT findings in one patient. American journal of neuroradiology 24: 1130–1132. PubMed ID: 12812938
  • Lieber DS, Hershman SG, Slate NG, Calvo SE, Sims KB, Schmahmann JD, Mootha VK. 2014. Next generation sequencing with copy-number-variant detection expands the phenotypic spectrum of HSD17B4-deficiency. BMC medical genetics 15: 30. PubMed ID: 24602372
  • Lines MA, Jobling R, Brady L, Marshall CR, Scherer SW, Rodriguez AR, Lee L, Lang AE, Mestre TA, Wanders RJ, Ferdinandusse S, Tarnopolsky MA; Canadian Pediatric Genetic Disorders Sequencing Consortium (FORGE Canada). 2014. Peroxisomal D-bifunctional protein deficiency: three adults diagnosed by whole-exome sequencing. Neurology 82: 963-968. PubMed ID: 24553428
  • McMillan HJ, Worthylake T, Schwartzentruber J, Gottlieb CC, Lawrence SE, MacKenzie A, Beaulieu CL, Mooyer PA, Wanders RJ, Majewski J, Bulman DE, Geraghty MT, Ferdinandusse S, Boycott KM. 2012. 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 7: 90. PubMed ID: 23181892
  • Mehtälä ML, Lensink MF, Pietikäinen LP, Hiltunen JK, Glumoff T. 2013. On the Molecular Basis of D-Bifunctional Protein Deficiency Type III. PLoS ONE 8: e53688. PubMed ID: 23308274
  • Pierce SB, Chisholm KM, Lynch ED, Lee MK, Walsh T, Opitz JM, Li W, Klevit RE, King M-C. 2011. Mutations in mitochondrial histidyl tRNA synthetase HARS2 cause ovarian dysgenesis and sensorineural hearing loss of Perrault syndrome. Proceedings of the National Academy of Sciences 108: 6543–6548. PubMed ID: 21464306
  • Pierce SB, Gersak K, Michaelson-Cohen R, Walsh T, Lee MK, Malach D, Klevit RE, King MC, Levy-Lahad E. 2013. Mutations in LARS2, encoding mitochondrial leucyl-tRNA synthetase, lead to premature ovarian failure and hearing loss in Perrault syndrome. American Journal of Human Genetics 92: 614-620. PubMed ID: 23541342
  • Pierce SB, Walsh T, Chisholm KM, Lee MK, Thornton AM, Fiumara A, Opitz JM, Levy-Lahad E, Klevit RE, King M-C. 2010. Mutations in the DBP-Deficiency Protein HSD17B4 Cause Ovarian Dysgenesis, Hearing Loss, and Ataxia of Perrault Syndrome. The American Journal of Human Genetics 87: 282–288. PubMed ID: 20673864
  • Van Grunsven EG, Mooijer PA, Aubourg P, Wanders RJ. 1999. Enoyl-CoA hydratase deficiency: identification of a new type of D-bifunctional protein deficiency. Hum. Mol. Genet. 8: 1509–1516. PubMed ID: 10400999


Ordering Options

We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.

myPrevent - Online Ordering

  • The test can be added to your online orders in the Summary and Pricing section.
  • Once the test has been added log in to myPrevent to fill out an online requisition form.
  • PGnome sequencing panels can be ordered via the myPrevent portal only at this time.

Requisition Form

  • A completed requisition form must accompany all specimens.
  • Billing information along with specimen and shipping instructions are within the requisition form.
  • All testing must be ordered by a qualified healthcare provider.

For Requisition Forms, visit our Forms page

If ordering a Duo or Trio test, the proband and all comparator samples are required to initiate testing. If we do not receive all required samples for the test ordered within 21 days, we will convert the order to the most effective testing strategy with the samples available. Prior authorization and/or billing in place may be impacted by a change in test code.

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