LRRK2 kinazında nadir biallelik fonksiyon kaybı varyantları interstisyel akciğer hastalığına neden olur

Araştırma özeti

Aşağıdaki metin kaynak makalenin lisansı doğrulanmış orijinal özetidir. cc by

Summary We report that biallelic LRRK2 loss-of-function (LoF) causes a Mendelian form of interstitial lung disease characterized by alveolar epithelial cell dysfunction and lung fibrosis in two brothers with a homozygous nonsense variant. Integrated clinical, imaging, histopathological, and biomarker analyses showed absent LRRK2 protein, reduced Rab10 phosphorylation, impaired alveolar type 2 cell function, and disrupted surfactant homeostasis. Consistent with a recessive genetic disorder, heterozygous LoF carriers have not been reported to have a lung phenotype. Additional biallelic LRRK2 LoF cases were identified in ILD cohorts, linking LRRK2 LoF to lung disease, in contrast to heterozygous activating missense variants that cause Parkinson’s disease (PD).

İlgili konular