DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for Perrault syndrome 7 — screening already-approved drugs against its 1-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease modulePerrault syndrome 7 maps to a 1-gene Open Targets module — the target space DeCure's AI scientist screens approved drugs against.
DeCure.ai methodSignature reversal (LINCS) plus network proximity (STRING) rank already-approved drugs likely to perturb this module — the same engine that produces DeCure.ai's repurposing hypotheses.
Repurposing thesisScreening approved medicines against this disease module, then publishing the evidence for the strongest candidate. Known pharmacology and human exposure data make the first question sharper — they do not establish safety or efficacy in a new indication.
Research record
01
ResearchComing soon
Candidate research + dossier — target rationale, drug-repurposing thesis and evidence pack.proof: Published dossier + on-chain hash
02
ValidationComing soon
In-vitro biological validation at a contract research org (CRO).proof: CRO contract + in-vitro report
03
Peer review & paperComing soon
Peer-reviewed paper published open-access (preprint + journal).proof: DOI + open-access link + on-chain hash
Current lead
No approved-drug candidate for perrault syndrome 7 is corroborated in the literature DeepSearch retrieved. Some conditions are managed with non-pharmacological care — a device, surgery or physical therapy — rather than a medicine; that may be the case here, or the literature we found may simply be too sparse yet to support a drug-repurposing angle.
What the evidence adds up to
Perrault syndrome is a rare autosomal recessive disorder first described in 1951, characterised by sensorineural hearing loss and primary ovarian insufficiency due to ovarian dysgenesis. A 2015 case report describes a sporadic case of Perrault syndrome with short stature and documented growth hormone deficiency, which the authors state is the first such documented case. They note the condition should be considered as a differential diagnosis when evaluating short stature with amenorrhea.
A 2022 review states that Perrault syndrome causes hearing loss in both men and women, usually affecting both ears, with first symptoms possible at birth or in infancy. The review identifies mutations in the TWNK, CLPP, HARS2, LARS2, and HSD17B4 genes as genetic causes of the syndrome.
A 2025 genotype-phenotype study of CLPP gene variants in Han Chinese families reports two families with Perrault syndrome type 3. Among 33 Perrault syndrome type 3 patients in the literature, 97% (31/32) had hearing loss, 55% (16/29) had neurological disease, and 71% (15/21) of females had primary ovarian insufficiency. Including four novel variants, 21 pathogenic CLPP gene variants have been reported, 57% missense and 43% truncating. Biallelic truncating or missense plus truncating genotypes showed higher rates of neurological disease (p = 0.001), but no significant difference in hearing loss incidence compared to biallelic missense genotypes. The study highlights challenges in diagnosis due to genetic and clinical heterogeneity.
No drug treatment is mentioned in any of these abstracts. What is still missing is any clinical trial testing a therapy, any patient stratification beyond genotype-phenotype correlations, and any funding directed toward treatment development for this rare disorder.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Journal of Pediatric Endocrinology and Metabolism · 2015 · 2 citations
Perrault syndrome with growth hormone deficiency: a rare autosomal recessive disorder
AbstractPerrault syndrome is a rare genetically heterogeneous autosomal recessive group of disorders described in 1951 by Perrault as gonadal dysgenesis with deafness. Here we present a rare case of sporadic Perrault syndrome with short stature and growth hormone deficiency (GHD). Although there was a report on partial GHD in Perrault, our case is a first of its kind with documented GHD (Nishi Y, Hamamoto K, Kajiyama M, Kawamura I. The Perrault syndrome: clinical report and review. Am J Med Genet 1988;31:623-9). We report this case because of the rarity of keeping this condition as a differential diagnosis while evaluating for short stature with amenorrhea.
Journal of Neuroscience and Neurological Research · 2022 · 2 citations · open access
The Role of Mutations on Genes TWNK, CLPP, HARS2, LARS2, HSD17B4 in Perrault Syndrome
AbstractPerrault syndrome was first reported by Dr. M. Perrault, a physician from Paris, in 1951. Perrault syndrome is a rare genetic disease that causes various signs and symptoms in men and women affected by this syndrome. One of the key features of this syndrome is hearing loss, which occurs in both men and women. In perrault syndrome, hearing problems occur due to changes in the inner ear, known as hearing loss. This disorder usually affects both ears of the patient and the first symptoms can start at birth or in infancy. Perrault syndrome has several genetic causes. However, researchers believe that perrault syndrome is caused by mutations in the TWNK, CLPP, HARS2, LARS2, and HSD17B4 genes.
CLPP Gene Variants Causing Perrault Syndrome Type 3 in Han Chinese Families: A Genotype-Phenotype Study
AbstractBACKGROUND: Perrault syndrome is a rare autosomal recessive disorder characterized by sensorineural hearing loss (SNHL) and primary ovarian insufficiency (POI) secondary to ovarian dysgenesis. However, the mutation spectrum of disease-causing genes for Perrault syndrome in the Chinese population remains poorly understood. In this study, we report on two Chinese families with Perrault syndrome type 3 caused by novel CLPP gene variants. We also conducted a comprehensive literature review of CLPP gene variants in Perrault syndrome type 3 to elucidate genotype-phenotype associations. METHODS: Using Whole Genome Sequencing (WGS) data, two pedigrees with Perrault syndrome type 3 were ascertained in the Chinese Deafness Genetics Cohort through genotype-driven analysis. Variants were validated using Sanger sequencing and copy number quantification methods. In vitro analysis of splice site variants in the CLPP gene using the minigene assay. RESULTS: Two Han Chinese families were ascertained: one with compound heterozygous variants (c.270 + 1G > C and c.355A > C [p. Ile119Leu]) and the other with missense variant (c.400G > C [p. Asp134His]) together with a large deletion in CLPP. In vitro minigene assays confirmed that the c.270 + 1G > C variant causes intron 2 retention and an alternative 5' splice site in exon 2, leading to protein alteration. Among 33 Perrault syndrome type 3 patients in literature, 97% (31/32) had hearing loss, 55% (16/29) neurological disease, and 71% (15/21) females had POI. Including our 4 novel variants, 21 pathogenic CLPP gene variants have been reported, with 57% (12/21) missense and 43% (9/21) truncating variants, mainly in the ATP-dependent Clp protease proteolytic subunit. Biallelic truncating or missense plus truncating genotypes showed higher rates of neurological disease (p = 0.001), but no significant difference in hearing loss incidence compared to biallelic missense genotypes was observed. CONCLUSION: This study highlights the challenges in diagnosing Perrault syndrome due to its genetically and clinically heterogeneity. By exploring novel variants and establishing genotype-phenotype correlations, we aim to improve the genetic diagnosis and consultation for this complex disorder.
Disease module: DeepOracle (Open Targets). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works (targeted per-candidate search), resolved on OpenAlex.
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