De Novo Heterozygous <i>KDM3B</i> Variants Expand the Mutational Spectrum of Diets-Jongmans Syndrome: Case Series and Literature Review

Early human evidence such as case series or small samples is exploring possible benefits.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Background Pathogenic variants in KDM3B have been implicated as the cause of Diets-Jongmans syndrome (DIJOS), an autosomal-dominant disorder characterized by growth retardation, intellectual disability, facial dysmorphism and autism-spectrum disorder. However, only a limited number of cases have been reported. Methods The general characteristics of four patients were recorded, including clinical features, child development, neuropsychological assessment and therapeutic interventions. Whole exome sequencing (WES) was performed for potential genetic causes and interpretation of variants was performed in accordance with ACMG guidelines. Results All patients carried de novo variants in the KDM3B gene, namely, c.2832-3C>G, c.1188del p.(Glu397Argfs*21), c.4580T>C p.(Leu1527Pro), and c.3220dup p.(Glu1074Glyfs*48). Unlike other patients with DIJOS who presented with growth retardation, mild to moderate intellectual developmental disorder and facial dysmorphism, our patients mainly presented with growth retardation, while their neurodevelopment was either normal or mildly impaired. In addition, our patients received primarily supportive care. One patient treated with recombinant human growth hormone (rhGH) showed improvement in growth. Conclusions Our results broaden the mutational spectrum of KDM3B -related disorder and highlight the inter-patient variability of the clinical phenotype.

Evidence level

Early human evidence such as case series or small samples is exploring possible benefits.

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