The following is a summary of “Premature Ovarian Insufficiency in CLPB Deficiency: Transcriptomic, Proteomic and Phenotypic Insights,” published in the December 2022 issue of Endocrinology & Metabolism by Tucker, et al.

Female infertility is frequently caused by premature ovarian insufficiency (POI), which typically manifests as a standalone disorder but can also be a component of other hereditary disorders. Comorbidity can be reduced, and health outcomes can be improved with early identification and treatment of POI. For a study, researchers sought to identify the genetic basis of syndromic POI, idiopathic neutropenia, cataracts, and intellectual impairment.

They carried out whole-exome sequencing (WES), followed by functional confirmation using RT-PCR, RNAseq, and quantitative proteomics, as well as clinical updates of patients with mutations in the caseinolytic peptidase B (CLPB) gene who had previously been reported.

They discovered causal variations in the mitochondrial disaggregase gene CLPB. Although there was probably a reporting bias toward severe cases, it was known that variations in the gene induced an autosomal recessive disease that included 3-methylglutaconic aciduria, neurological impairment, cataracts, and neutropenia and is frequently fatal in childhood. They confirmed causality and learned more about the genotype: phenotype link using RNAseq and quantitative proteomics. Infertility and POI were shown to be prevalent postpubertal illnesses in the clinical follow-up of CLPB-deficient patients who lived to maturity.

CLPB deficiency was linked to a new splicing variation in a child that lived to maturity. Women who were postpubertal and had a CLPB deficit frequently exhibited POI. To reduce related comorbidities, patients with CLPB deficiency should be directed to pediatric gynecologists/endocrinologists for quick POI diagnosis and hormone replacement treatment.