UNASSIGNED: Wilson disease is a rare genetic disorder, characterised by excessive deposition of copper in the liver, brain, and other tissues. Penicillamine, a copper-chelating agent, is used in high doses in the treatment of Wilson disease leading to a variety of cutaneous reactions, including hyper-sensitivity reactions, pseudoxanthoma elasticum, elastosis perforans serpiginosa, anetoderma, and cutis laxa (CL). We present a rare case of localised CL induced by penicillamine for Wilson disease, in the absence of elastosis perforans serpiginosa.
UNASSIGNED: A 41-year-old male with Wilson disease treated with long-term high-dose penicillamine was referred to us for a basal cell carcinoma on the scalp. On physical examination, diffusely flaccid and redundant skin on the right side of the neck were observed. Histopathology revealed findings consistent with CL.
UNASSIGNED: Long-term treatment with penicillamine for Wilson disease may induce localized CL, possibly by direct inhibition of cross-linkage of collagen fibres.

暂无摘要。

BACKGROUND: Cutis laxa is a connective tissue disease caused by abnormal synthesis or secretion of skin elastic fibers, leading to skin flabby and saggy in various body parts. It can be divided into congenital cutis laxa and acquired cutis laxa, and inherited cutis laxa syndromes is more common in clinic.
METHODS: In this study, we reported a case of a Han-Chinese male newborn with ATP6V0A2 gene variant leading to cutis laxa. The proband was identified by whole-exome sequencing to determine the novel variant, and their parents were verified by Sanger sequencing. Bioinformatics analysis and minigene assay were used to verify the effect of this variant on splicing function.
RESULTS: The main manifestations of the proband are skin laxity, abnormal facial features, and enlargement of the anterior fontanelle. Whole-exome sequencing showed that the newborn carried a non-canonical splicing-site variant c.117 + 5G > T, p. (?) in ATP6V0A2 gene. Sanger sequencing showed that both parents of the proband carried the heterozygous variant. The results of bioinformatics analysis and minigene assay displayed that the variant site affected the splicing function of pre-mRNA of the ATP6V0A2 gene.
CONCLUSIONS: In this study, it was identified that ATP6V0A2 gene c. 117 + 5G > T may be the cause of the disease. The non-canonical splicing variants of ATP6V0A2 gene were rarely reported in the past, and this variant expanded the variants spectrum of the gene. The functional study of minigene assay plays a certain role in improving the level of evidence for the pathogenicity of splicing variants, which lays a foundation for prenatal counseling and follow-up gene therapy.

暂无摘要。

Vacuolar ATPases (V-ATPases), proton pumps composed of 16 subunits, are necessary for a variety of cellular functions. Subunit \"a\" has four isoforms, a1-a4, each with a distinct cellular location. We identified a phosphoinositide (PIP) interaction motif, KXnK(R)IK(R), conserved in all four isoforms, and hypothesize that a/PIP interactions regulate V-ATPase recruitment/retention to different organelles. Among the four isoforms, a2 is enriched on Golgi with a2 mutations in the PIP motif resulting in cutis laxa. We hypothesize that the hydrophilic N-terminal (NT) domain of a2 contains a lipid-binding domain, and mutations in this domain prevent interaction with Golgi-enriched PIPs, resulting in cutis laxa. We recreated the cutis laxa-causing mutation K237_V238del, and a double mutation in the PIP-binding motif, K237A/V238A. Circular dichroism confirmed that there were no protein structure alterations. Pull-down assays with PIP-enriched liposomes revealed that wildtype a2NT preferentially binds phosphatidylinositol 4-phosphate (PI(4)P), while mutants decreased binding to PI(4)P. In HEK293 cells, wildtype a2NT was localized to Golgi and co-purified with microsomal membranes. Mutants reduced Golgi localization and membrane association. Rapamycin depletion of PI(4)P diminished a2NT-Golgi localization. We conclude that a2NT is sufficient for Golgi retention, suggesting the lipid-binding motif is involved in V-ATPase targeting and/or retention. Mutational analyses suggest a molecular mechanism underlying how a2 mutations result in cutis laxa.

暂无摘要。

Cutis laxa is a rare connective tissue disorder, characterized by a reduced number and abnormal properties of elastic fibers throughout the dermis, creating a clinical appearance of premature aging. It can be subdivided into inherited and acquired, the latter rarer than the former, and skin involvement may be localized or generalized. The etiology of acquired cutis laxa (ACL) remains unknown and there is no definitive treatment. We present the case of a 30-year-old man diagnosed with type I ACL with progressive systemic involvement at the renal, pulmonary, and digestive levels. Histological analysis of the skin revealed reduction and fragmentation of elastic fibers. Immunosuppressive treatment was started with prednisone, cyclophosphamide, and rituximab, with which a complete response to proteinuria was achieved and the progression of lung damage was limited. Autoimmune, infectious, and neoplastic diseases were ruled out.

暂无摘要。

Genetic variants in ATP7A are associated with a spectrum of X-linked disorders. In descending order of severity, these are Menkes disease, occipital horn syndrome, and X-linked distal spinal muscular atrophy. After 30 years of diagnostic investigation, we identified a deep intronic ATP7A variant in four males from a family affected to variable degrees by a predominantly skeletal phenotype, featuring bowing of long bones, elbow joints with restricted mobility which dislocate frequently, coarse curly hair, chronic diarrhoea, and motor coordination difficulties. Analysis of whole genome sequencing data from the Genomics England 100,000 Genomes Project following clinical re-evaluation identified a deep intronic ATP7A variant, which was predicted by SpliceAI to have a modest splicing effect. Using a mini-gene splicing assay, we determined that the intronic variant results in aberrant splicing. Sanger sequencing of patient cDNA revealed ATP7A transcripts with exon 5 skipping, or inclusion of a novel intron 4 pseudoexon. In both instances, frameshift leading to premature termination are predicted. Quantification of ATP7A mRNA transcripts using a qPCR assay indicated that the majority of transcripts (86.1 %) have non-canonical splicing, with 68.0 % featuring exon 5 skipping, and 18.1 % featuring the novel pseudoexon. We suggest that the variability of the phenotypes within the affected males results from the stochastic effects of splicing. This deep intronic variant, resulting in aberrant ATP7A splicing, expands the understanding of intronic variation on the ATP7A-related disease spectrum.

BACKGROUND: Traditional facelift surgery does not behave well in the correction of nasolabial folds, which is a common clinical problem and needed to be improved.
OBJECTIVE: To investigate the effect of free dermal fat grafting during facelift surgery for the treatment of nasolabial folds.
METHODS: This prospective cohort study involved 80 patients with moderate to severe nasolabial folds and facial skin dermatolysis. Fifty of them underwent facelift surgery combined with free dermal fat grafting, and 30 of them underwent traditional facelift surgery. These patients were followed up 2 months, 6 months, and 1 year after the surgery to evaluate the effect.
RESULTS: The difference in Wrinkle Severity Rating Scale (WSRS) scores, assessed at each follow-up, between the patients who underwent and did not undergo free dermal fat grafting during facelift surgery, was statistically significant. For patients who underwent free dermal fat grafting during facelift surgery, the WSRS scores assessed at 2 months, 6 months, and 1 year after the surgery were significantly different from those before the surgery. The analytic results of FACE-Q indicated a high level of overall satisfaction rate. No major complications were recorded.
CONCLUSIONS: Free dermal fat as a filler for nasolabial folds can achieve excellent therapeutic effect. The combination of facelift surgery with free dermal fat grafting for the treatment of nasolabial folds can provide very good long-term results and a high patient satisfaction rate for patients with symptoms of facial aging such as facial dermatolysis, obvious wrinkles, and deep nasolabial folds.
METHODS: