Variants S206R and L541P have reduced basal ATPase and S206R shows little, and L541P shows no, stimulation by retinal (Fig. 4a).
L541P was purified, reconstituted into membranes, and tested for basal and retinal-stimulated ATPase activities. L541P was shown to have reduced basal ATPase, and no stimulation by retinal (Fig 4a)
both the P and PV ABCA4 variants exhibited a dramatically reduced basal ATPase activity (∼30% of WT ABCA4), which did not increase upon the addition of all-trans-retinal. Thus, ABCA4 variants carrying the P mutation were functionally impaired.
ATPase activity in HEK293 cells showed severely reduced basal ATPase activity, ∼30% of WT ABCA4, indicating that this variant impacts protein function (PS3_Supporting; PMIDs).
Amounts of A2E in the eyes of Abca4PV/PV, Abca4−/− and WT mice at the ages of 1, 3, 6, 12 and 15 months were quantified by reverse-phase high-performance liquid chromatography (HPLC) (Fig. 9B). Mice were raised under a regular 12-h light (∼10 lux)/12-h dark cycle. Age-dependent A2E accumulation was noted in all genotypes, with Abca4PV/PV and Abca4−/− mice accumulating about 5-fold more A2E than WT mice. No statistically significant differences in A2E accumulation were found between Abca4PV/PV and Abca4−/− animals.
Autofluorescence and A2E production was measured in transgenic mice and showed loss of function of ABCA4 protein indicating that this variant impacts protein function (PS3; PMIDs).
Your eyes do not deceive you: Sony's nearly decades-old console has received a new update. Version 4.93 of the PS3 firmware is now available for anyone still kicking around on the company's decidedly retro home system, though you shouldn't expect a lot from the update.This update is the latest in an annual trend. Once a year for the last several years, Sony has updated the PS3 firmware and every time, the system's patch notes have trotted out the same line: "This system software update improves system performance."
PlayStation 3 received an update in March 2026 to allow people to continue using it as a Blu-Ray player. It was first released in November 2006.
Disease: Myopathic Ehlers-Danlos Syndrome (mEDS)
Patient(s): 47 yo male, japanese descent
Variant: COL12A1 NM_004370.6: c.395-1G>A (Homozygous variant, at splice acceptor site in exon 6, causes in-frame skipping)(located in the genomic region encoding the first von Willebrand factor A domain)
Family: consanguineous parents with no related features of mEDS, healthy older brother
Phenotypes (Childhood): hypotonia, weak spontaneous movements, scoliosis, torticollis, soft plams, undescended testes, motor developmental delay, slender build, triangular face, short palpebral fissures, small nose, small mouth, large ears, bilateral knee dislocations, short stature.
Phenotypes (Adulthood): short stature, high palate, hypermobile small joints, deformed cervical spine, brachycephaly, bilateral long deformed 5th finger, severe scoliosis post surgical fixation, asymmetric pelvis
Classification: sequencing panel found the variant and it was confirmed through sanger sequencing.
According to ClinGenSVI recommendation: PVS1_Strong
Applicable criteria:
1) the one at a GT-AG 1,2 splice site
2) the one exerting exon skipping or use of a crypic splice site that preserved the reading frame.
3) the one at a truncated/altered region critical to protein function; was classified as PM3_Supporting (homozygous)
Variant not registered in gnomAD (PM2_Supporting)
Partial defect of first vWA in collagen XII judged as PS3