We report statistically significant overrepresentation of pathogenic variants for several Mendelian disorders, including phenylketonuria (PAH, rs5030858), Wilson's disease (ATP7B, rs76151636), factor VII deficiency (F7, rs36209567), kyphoscoliosis type of Ehlers-Danlos syndrome (FKBP14, rs542489955), and several other recessive pathologies.
For the first patient, a liver biopsy confirmed the pathological features of CHF, and genetic testing revealed three heterozygous missense mutations, which were classified as "undetermined" in the public Wilson's disease/ATP7B and ADPKD/PKD1 databases.
The underlying mechanisms of CHM for WD are associated with reversing the ATP7B mutants, exerting anti-oxidation, anti-inflammation, and anti-hepatic fibrosis effects.
In this review, the genetic bases of the disease are discussed, with emphasis on the role of ATP7B (the Wilson disease protein) dysfunction as a determinant factor of systemic copper overload.
In humans, the Cu chaperone Atox1 mediates Cu(I) delivery to P-type ATPases Atp7a and Atp7b (the Menkes and Wilson disease proteins, respectively), which are responsible for Cu release to the secretory pathway and excess Cu efflux.
Intravenously administering an adeno-associated viral (AAV) 8 vector expressing a codon-optimized version of the human ATP7B transgene into 2-month-old WD mice significantly decreased liver copper levels compared with age-matched, uninjected, WD mice.
Wilson disease (WD) is a hereditary metabolic disorder (HMD) caused by a mutation in the copper-transporting gene ATP7B affecting the liver and central nervous system.
Generation of an integration-free induced pluripotent stem cell (iPSC) line (ZZUNEUi003-A) from a Wilson's disease patient harboring a homozygous R778L mutation in ATP7B gene.
We aimed to (1) perform a meta-analysis of previous WD prevalence estimates, (2) estimate the prevalence of WD from population sequencing data, and (3) generate an ATP7B gene variant database.
A WGBS comparison of human WD liver and tx-j mouse liver demonstrated a significant overlap of differentially methylated genes associated with ATP7B deficiency.
<b>Objectives:</b> To assess the impact of molecularly expressed ATP7B gene products in order to assist diagnosis of Wilson disease in pediatric patients having a novel mutation and subtle neuropsychiatric disease.
To estimate the genetic prevalence of WD in France, we analysed the ATP7B gene by Next Generation Sequencing from a large French cohort of indiscriminate subjects.