The American Journal of Human Genetics· 2026Q1
Androgens mediate sexual dimorphism in Pilarowski-Bjornsson syndrome
- 2citations
- Q1SCImago
- 2026year
Short summary
Androgens modulate the expression of Pilarowski-Bjornsson syndrome (PILBOS) features, with testosterone rescuing phenotypes in females and orchiectomy unmasking them in males.
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Key points
- PILBOS, a neurodevelopmental disorder, shows sexual dimorphism, with males being overrepresented despite initial descriptions in females.
- A mouse model (Chd1 R616Q/+) displays female-restricted growth deficiency, anxiety, and hypotonia.
- Orchiectomy in male mice unmasks growth deficiency, while testosterone administration rescues phenotypes in female mice.
- Human genetic databases show an overrepresentation of rare missense variants in CHD1 in males, suggesting a male-protective effect.
AI-generated from the title and abstract; the full text is not read.
Abstract
Abstract Sex-specific penetrance in autosomal dominant Mendelian conditions is largely understudied. The neurodevelopmental disorder Pilarowski-Bjornsson syndrome (PILBOS) was initially described in females. Here, we describe the clinical and genetic characteristics of the largest PILBOS cohort to date, showing that both sexes can exhibit PILBOS features, although males are overrepresented. A mouse model carrying a human-derived Chd1 missense variant ( Chd1 R 616 Q /+ ) displays female-restricted phenotypes, including growth deficiency, anxiety and hypotonia. Orchiectomy unmasks a growth deficiency phenotype in male Chd1 R 616 Q /+ mice, while testosterone rescues the phenotype in females, implicating androgens in phenotype modulation. In the gnomAD and UK Biobank databases, rare missense variants in CHD1 are overrepresented in males, supporting a male protective effect. We identify 33 additional highly constrained autosomal genes with missense variant overrepresentation in males. Our results support androgen-regulated sexual dimorphism in PILBOS and open novel avenues to understand the mechanistic basis of sexual dimorphism in other autosomal Mendelian disorders. Graphical Abstract
The authors' abstract, as published at the source. The American Journal of Human Genetics, 2026 · DOI ↗
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Field: Genetics (Biochemistry, Genetics and Molecular Biology)
GeneticsBiochemistry, Genetics and Molecular Biology