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Dermatology Practical & Conceptual Jan 2023Poikiloderma of Civatte (PC) is a common, acquired, chronic, benign poikiloderma of the neck and face, most commonly affecting peri-menopausal females. At the time of...
INTRODUCTION
Poikiloderma of Civatte (PC) is a common, acquired, chronic, benign poikiloderma of the neck and face, most commonly affecting peri-menopausal females. At the time of writing, few studies have been published regarding the dermoscopy of PC.
OBJECTIVE
To describe the dermoscopic picture of PC, so as to provide a clinico dermoscopic diagnosis and differential diagnosis for PC.
METHODS
Twenty-eight patients with PC, aged 26-73 years, of whom 19 females (67.86%) were evaluated by detailed history, clinical examination, and dermoscopic examination with hand-held dermoscope.
RESULTS
The reticular pattern was observed in 15 cases (53.6%); the white dot in 10 (35.7%); the non-specific in 9 (32.1%); and the combination of linear and dotted vessels in 8 (28.6%). Regarding local dermoscopic features, converging curved vessels were observed in 18 cases (64.3%); linear irregular vessels in 17 (60.7%); rhomboidal/polygonal vessels in 15 (53.6%); dotted/globular vessels in 10 (35.7%); white macules in 23 (82.1%); brown macules in 11 (39.3%); and whitish follicular plugs in 6 (21.4%).
CONCLUSIONS
The dermoscopic picture of PC is highly characteristic and corresponds well to both clinical and histological findings. Dermoscopy may assist clinical diagnosis, as well as the differentiation from other dermatoses of the neck and face, especially poikilodermas with guarded prognosis.
PubMed: 36892344
DOI: 10.5826/dpc.1301a7 -
Frontiers in Immunology 2023Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) and poikiloderma in association with tendon contractures, myopathy, and pulmonary fibrosis...
INTRODUCTION
Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) and poikiloderma in association with tendon contractures, myopathy, and pulmonary fibrosis (POIKTMP) are rare inherited syndromes resulting from biallelic pathogenic variants in and heterozygous pathogenic variants in , respectively. The clinical diagnosis of APECED and POIKTMP rely on the development of two or more characteristic disease manifestations that define the corresponding syndromes. We discuss the shared and distinct clinical, radiographic, and histological features between APECED and POIKTMP presented in our patient case and describe his treatment response to azathioprine for POIKTMP-associated hepatitis, myositis, and pneumonitis.
METHODS
Through informed consent and enrollment onto IRB-approved protocols (NCT01386437, NCT03206099) the patient underwent a comprehensive clinical evaluation at the NIH Clinical Center alongside exome sequencing, copy number variation analysis, autoantibody surveys, peripheral blood immunophenotyping, and salivary cytokine analyses.
RESULTS
We report the presentation and evaluation of a 9-year-old boy who was referred to the NIH Clinical Center with an APECED-like clinical phenotype that included the classic APECED dyad of CMC and hypoparathyroidism. He was found to meet clinical diagnostic criteria for POIKTMP featuring poikiloderma, tendon contractures, myopathy, and pneumonitis, and exome sequencing revealed a c.1292T>C heterozygous pathogenic variant in but no deleterious single nucleotide variants or copy number variants in .
DISCUSSION
This report expands upon the available genetic, clinical, autoantibody, immunological, and treatment response information on POIKTMP.
Topics: Male; Humans; DNA Copy Number Variations; Polyendocrinopathies, Autoimmune; Autoantibodies; Azathioprine; Phenotype; Cell Cycle Proteins
PubMed: 36875114
DOI: 10.3389/fimmu.2023.1133387 -
Science (New York, N.Y.) Mar 2023Mutations in the 3' to 5' RNA exonuclease USB1 cause hematopoietic failure in poikiloderma with neutropenia (PN). Although USB1 is known to regulate U6 small nuclear RNA...
Mutations in the 3' to 5' RNA exonuclease USB1 cause hematopoietic failure in poikiloderma with neutropenia (PN). Although USB1 is known to regulate U6 small nuclear RNA maturation, the molecular mechanism underlying PN remains undetermined, as pre-mRNA splicing is unaffected in patients. We generated human embryonic stem cells harboring the PN-associated mutation c.531_delA in USB1 and show that this mutation impairs human hematopoiesis. Dysregulated microRNA (miRNA) levels in USB1 mutants during blood development contribute to hematopoietic failure, because of a failure to remove 3'-end adenylated tails added by PAPD5/7. Modulation of miRNA 3'-end adenylation through genetic or chemical inhibition of PAPD5/7 rescues hematopoiesis in USB1 mutants. This work shows that USB1 acts as a miRNA deadenylase and suggests PAPD5/7 inhibition as a potential therapy for PN.
Topics: Humans; Hematopoiesis; Human Embryonic Stem Cells; MicroRNAs; Neutropenia; Phosphoric Diester Hydrolases; Mutation
PubMed: 36862787
DOI: 10.1126/science.abj8379 -
Annales de Dermatologie Et de... Jun 2023
Topics: Humans; Dermatitis, Exfoliative; Dermatomyositis; Mycosis Fungoides; Myositis; Skin Neoplasms
PubMed: 36682974
DOI: 10.1016/j.annder.2021.04.011 -
Calcified Tissue International Apr 2023Progressive osseous heteroplasia (POH) is a rare, debilitating disorder characterized by heterotopic ossification in the skin and muscles, resulting in contractures of...
INTRODUCTION
Progressive osseous heteroplasia (POH) is a rare, debilitating disorder characterized by heterotopic ossification in the skin and muscles, resulting in contractures of the joints and progressive loss of function. While 60-70% of the POH patients have paternally inherited, inactivating pathogenic variants in GNAS, the remaining 30-40% have no known etiology. FAM111B pathogenic variants, located on chromosome 11q12.1, cause POIKTMP (hereditary fibrosing poikiloderma with tendon contractures, myopathy, and pulmonary fibrosis), a very rare, autosomal-dominant disorder with high frequency of de novo missense pathogenic variants, which affects multiple tissues and organs, causing extensive fibrosis and muscle adiposis, though the exact mechanism is unknown. To our knowledge, there are no reports of FAM111B associated with POH. We describe the first case of POH phenotype associated with a novel de novo frameshift pathogenic variant in the FAM111B and present an analysis of the protein structure and function caused by this genomic disruption.
CASE
A 15-year-old African-American male presented with generalized calcific nodules, progressive contractures, and muscle weakness leading to immobility, beginning at 6 years of age. Cutaneous examination showed generalized hard nodules varying from small to plaque-like ulcerated erupted skin lesions. Biochemical evaluation revealed 25(OH) vitamin D insufficiency (20 ng/mL), and normal levels of parathyroid hormone, FGF-23, alkaline phosphatase, calcium, and phosphorus. Skeletal survey radiographs and computed tomography (CT) of the chest, abdomen, and pelvis showed extensive soft tissue and muscle heterotopic ossifications involving shoulders, axillae, trunk, abdomen, pelvis, upper and lower extremities, in a clumped, conglomerate distribution within muscle, subcutaneous fat, and in some areas extending to the skin. There was no pulmonary fibrosis on the chest CT. The clinical and radiographic findings were most consistent with POH. A trio-clinical exome sequencing revealed a de novo heterozygous likely pathogenic variant in the FAM111B (OMIM # 615584) (c.1462delT [p.Cys488Valfs*21]). The resulted frameshift change in exon 4 replaced C-terminal region with 21 alternative amino acids. Multiple, previously reported disease-associated variants appear to localize within the trypsin-like cysteine/serine peptidase domain in which this variant occurs, supporting the functional significance of this region, though none have been previously reported to be associated with POH phenotype. Our 3D protein modeling showed obliteration of predicted protein folding and structure, and elimination of the zinc-binding domain, likely severely affecting protein function.
CONCLUSION
This is the first case of POH phenotype associated with a novel de novo pathogenic frameshift variant in FAM111B. Whether the frameshift change in FAM111B predicts POH remains unclear. Further evaluations are necessary to fully elucidate this finding and the potential role and mechanism by which the FAM111B variants contributes to POH phenotype.
Topics: Male; Humans; GTP-Binding Protein alpha Subunits, Gs; Ossification, Heterotopic; Phenotype; Contracture; Fibrosis; Cell Cycle Proteins
PubMed: 36575358
DOI: 10.1007/s00223-022-01053-0 -
American Journal of Medical Genetics.... Jan 2023Rothmund-Thomson syndrome (RTS) is a rare autosomal recessive disorder characterized by a rash that progresses to poikiloderma. Other common features include sparse...
Rothmund-Thomson syndrome (RTS) is a rare autosomal recessive disorder characterized by a rash that progresses to poikiloderma. Other common features include sparse hair, eyelashes and eyebrows, short stature, variable skeletal abnormalities, dental defects, cataracts, hypogonadism, and an increased risk for cancer, especially osteosarcoma and skin cancer. RTS is caused by biallelic pathogenic variants in ANAPC1 (Type 1 RTS) or RECQL4 (Type 2 RTS). We present an African girl with Type 2 RTS caused by a nonsense variant and an intronic variant in RECQL4. The patient presented precocious puberty, which has not been previously reported in RTS and that was treated with a GnRH analog, and anal stenosis, which has only been reported once. This case highlights the need to consider deep intronic variants in patients with RTS when pathogenic variants in the coding regions and exon/intron boundaries are not identified and expands the phenotypic spectrum of this disorder.
Topics: Female; Humans; Rothmund-Thomson Syndrome; Constriction, Pathologic; RecQ Helicases; Osteosarcoma; Mutation; Puberty, Precocious; Bone Neoplasms
PubMed: 36164748
DOI: 10.1002/ajmg.a.62980 -
Dermatology Practical & Conceptual Jul 2022Dermoscopy is a noninvasive and easy to apply technique that allows in vivo magnification of the skin and thus observation of morphologic structures invisible to the...
INTRODUCTION
Dermoscopy is a noninvasive and easy to apply technique that allows in vivo magnification of the skin and thus observation of morphologic structures invisible to the naked eye. Recently, it gained popularity for evaluation of inflammatory skin conditions. In the field of connective tissue diseases, dermoscopy has been used mainly as a simple and accessible substitute of nailfold capillaroscopy.
OBJECTIVES
The aim of the present study is to expand the application of dermoscopy in patients with dermatomyositis (DM) beyond the usual nailfold examination. A clinico-dermoscopic correlation between clinical signs of skin affection and dermoscopic features is also suggested.
METHODS
A total of 29 patients with DM were enrolled in this descriptive prospective study, conducted over a 3-year period. Dermoscopy was performed by a DermLite DL1 dermatoscope on polarization mode, attached to One Plus 3T camera. The following skin lesions were examined: periungual affection, scalp DM, Gottron papules, palmar papules, poikiloderma and auricular changes.
RESULTS
Dermoscopy detected predominantly advanced nail fold capillary changes - giant capillaries (79%), microhemorrhages (46%) and avascular areas (25%). The most prevalent trichoscopic features were enlarged tortuous capillaries (64%), interfollicular scales (50%) and peripilar casts and tufting (36%). Among the other skin lesions assessed in this study - Gottron papules were present in 20 patients, poikiloderma in 11, palmar papules in 4 and auricular lesions in 4 patients.
CONCLUSIONS
The use of dermoscopy for clinical evaluation of skin lesions in DM enhances diagnostic accuracy and elucidates poorly known characteristics of the disease.
PubMed: 36159137
DOI: 10.5826/dpc.1203a142 -
Pediatric Dermatology Jan 2023Hereditary fibrosing poikiloderma with tendon contractures, myopathy, and pulmonary fibrosis (POIKTMP) is a genodermatosis with autosomal dominant inheritance caused by... (Review)
Review
Hereditary fibrosing poikiloderma with tendon contractures, myopathy, and pulmonary fibrosis (POIKTMP) is a genodermatosis with autosomal dominant inheritance caused by mutations in FAM111B. We report another case with a new pathogenic variant and analyze all previously published 34 cases with a focus on sequence of clinical presentation and genotype-phenotype correlation. POIKTMP is characterized by marked age-dependent clinical expressivity. FAM111B encodes a catalytic nuclear protein, expressed in many tissues, which contributes to impaired DNA repair affecting multiple systems. Specific inhibition of catalytic activity might be a future strategy to halt progression of this otherwise untreatable disease. Given the relentless progression of the disease, it would make sense to start such treatment as early as possible. In order to achieve this objective, children with suspected POIKTMP should therefore undergo early imaging of all relevant organ systems.
Topics: Humans; Pulmonary Fibrosis; Cell Cycle Proteins; Contracture; Mutation; Atrophy; Tendons; Phenotype
PubMed: 36102338
DOI: 10.1111/pde.15133 -
Frontiers in Genetics 2022Congenital poikiloderma is an extremely rare autosomal dominant genetic syndrome, characterized by a combination of early onset poikiloderma, telangiectasia, and...
Congenital poikiloderma is an extremely rare autosomal dominant genetic syndrome, characterized by a combination of early onset poikiloderma, telangiectasia, and epidermal atrophy. gene with multiple mutations has been identified as a potential causative gene for congenital poikiloderma. In this report, we described a boy with congenital poikiloderma confirmed by clinical manifestations. Next-generation sequencing based on a gene probe panel consisting of 541 genetic loci of genodermatoses, was used to screen mutations of the proband and his parents. Results showed that a missense mutation in the gene c.1883G>A (rs587777238) was identified in the proband, but absent in his parents, indicating the mutation is . In conclusion, a new case of congenital poikiloderma in China was reported, and the hotspot mutations in codon 628 of gene was reviewed, as well as authenticating the uncertain association between genotypes and phenotypes in this rare disease.
PubMed: 36092869
DOI: 10.3389/fgene.2022.926451