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Frontiers in Genetics 2023
Commentary: Case report: Hereditary fibrosing poikiloderma with tendon contractures, myopathy, and pulmonary fibrosis (POIKTMP) presenting with liver cirrhosis and steroid-responsive interstitial pneumonia.
PubMed: 38188503
DOI: 10.3389/fgene.2023.1255807 -
Frontiers in Aging 2023Rothmund-Thomson syndrome (RTS) is a rare autosomal recessive disorder characterized by a range of clinical symptoms, including poikiloderma, juvenile cataracts, short... (Review)
Review
Rothmund-Thomson syndrome (RTS) is a rare autosomal recessive disorder characterized by a range of clinical symptoms, including poikiloderma, juvenile cataracts, short stature, sparse hair, eyebrows/eyelashes, nail dysplasia, and skeletal abnormalities. While classically associated with mutations in the gene, which encodes a DNA helicase involved in DNA replication and repair, three additional genes have been recently identified in RTS: , encoding a subunit of the APC/C complex; which encodes a nuclease/helicase involved in DNA repair; and , encoding a poorly characterized protein implicated in excitatory synapse formation and splicing. Here, we review the clinical spectrum of RTS patients, analyze the genetic basis of the disease, and discuss molecular functions of the affected genes, drawing some novel genotype-phenotype correlations and proposing avenues for future studies into this enigmatic disorder.
PubMed: 38021400
DOI: 10.3389/fragi.2023.1296409 -
British Journal of Haematology Feb 2024The clinical problem of a non-healing fistula in ano in a child affected with poikiloderma with neutropenia (PN) was the stimulus for an innovative study by Parajuli...
The clinical problem of a non-healing fistula in ano in a child affected with poikiloderma with neutropenia (PN) was the stimulus for an innovative study by Parajuli et al. that sheds light on the pathological mechanisms in this disease. Multiparametric analyses of the patient's blood mononuclear cells by cell culture, flow cytometry and multiplex cytokine assay suggested a block of monocyte differentiation. Monocyte transcriptome profiling revealed a signature consistent with the haematological picture and the clinical presentation. Commentary on: Parajuli et al. Defective monocyte plasticity and altered cAMP pathway characterize USB1-mutated poikiloderma with neutropenia Clericuzio type. Br J Haematol 2024;204:683-693.
Topics: Child; Humans; Skin Abnormalities; Neutropenia; Monocytes; Mutation; Phosphoric Diester Hydrolases
PubMed: 37932156
DOI: 10.1111/bjh.19184 -
Clinical and Experimental Dermatology Feb 2024
Topics: Humans; Epidermolysis Bullosa; Blister; Periodontal Diseases; Photosensitivity Disorders; Mutation
PubMed: 37878805
DOI: 10.1093/ced/llad364 -
Annals of Dermatology May 2023Subcutaneous panniculitis-like T-cell lymphoma (SPTL) is an extremely rare, indolent skin malignancy that can be difficult to distinguish from autoimmune...
Subcutaneous panniculitis-like T-cell lymphoma (SPTL) is an extremely rare, indolent skin malignancy that can be difficult to distinguish from autoimmune disease-associated panniculitides. Here, we describe a 12-year-old boy who was diagnosed at age 7 years with dermatomyositis with classical manifestations, including poikiloderma, Gottron's sign, and symmetric muscle weakness. Recently, the boy presented multiple subcutaneous nodules and fever. Histopathological examination and immunohistochemical staining revealed coexistence of SPTL. To our knowledge, this is the first case of dermatomyositis accompanied with SPTL. This case alert clinical physicians of the possibility of SPTL should be considered when a patient with dermatomyositis has new lesions presenting as nodules and unknown fever.
PubMed: 37853872
DOI: 10.5021/ad.20.310 -
Pediatric Dermatology 2023Epidermolysis bullosa (EB) features skin and mucosal fragility due to pathogenic variants in genes encoding components of the cutaneous basement membrane. Based on the...
BACKGROUND
Epidermolysis bullosa (EB) features skin and mucosal fragility due to pathogenic variants in genes encoding components of the cutaneous basement membrane. Based on the level of separation within the dermal-epidermal junction, EB is sub-classified into four major types including EB simplex (EBS), junctional EB (JEB), dystrophic EB (DEB), and Kindler EB (KEB) with 16 EB-associated genes reported to date.
METHODS
We ascertained a cohort of 151 EB patients of various Middle Eastern ethnic backgrounds.
RESULTS
The cohort was comprised of EBS (64%, 97/151), DEB (21%, 31/151), JEB (12%, 18/151), and KEB (3%, 5/151). KRT14 and KRT5 variants were most common among EBS patients with 43% (42/97) and 46% (45/97) of EBS patients carrying mutations in either of these two genes, respectively. Truncal involvement was more common in KRT14-associated EBS as compared to EBS due to KRT5 mutations (p < .05). Mutations in COL17A1 and laminin 332-encoding genes were identified in 55% (10/18) and 45% (8/18) of JEB patients. Scarring alopecia, caries, and EB nevi were most common among JEB patients carrying COL17A1 mutations as compared to laminin 332-associated JEB (p < .05). Abnormal nails were evident in most DEB and JEB patients while poikiloderma was exclusively observed in KEB (p < .001).
CONCLUSIONS
EB patients of Middle Eastern origin were found to feature specific phenotype-genotype correlations of relevance to the diagnosis and genetic counseling of patients in this region.
Topics: Humans; Epidermolysis Bullosa; Epidermolysis Bullosa, Junctional; Epidermolysis Bullosa Dystrophica; Skin; Epidermolysis Bullosa Simplex
PubMed: 37827535
DOI: 10.1111/pde.15440 -
British Journal of Haematology Feb 2024Poikiloderma with neutropenia (PN) Clericuzio type (OMIM #604173) is a rare disease with areas of skin hyper- and hypopigmentation caused by biallelic USB1 variants. The...
Poikiloderma with neutropenia (PN) Clericuzio type (OMIM #604173) is a rare disease with areas of skin hyper- and hypopigmentation caused by biallelic USB1 variants. The current study was spurred by poor healing of a perianal tear wound in one affected child homozygous for c.266-1G>A (p.E90Sfster8) mutation, from a family reported previously. Treatment with G-CSF/CSF3 or GM-CSF/CSF2 transiently increased neutrophil/monocytes count with no effect on wound healing. Analysis of peripheral blood revealed a lack of non-classical (CD14 CD16 ) monocytes, associated with a systemic inflammatory cytokine profile, in the two affected brothers. Importantly, despite normal expression of cognate receptors, monocytes from PN patients did not respond to M-CSF or IL-34 in vitro, as determined by cytokine secretion or CD16 expression. RNAseq of monocytes showed 293 differentially expressed genes, including significant downregulation of GATA2, AKAP6 and PDE4DIP that are associated with leucocyte differentiation and cyclic adenosine monophosphate (cAMP) signalling. Notably, the plasma cAMP was significantly low in the PN patients. Our study revealed a novel association of PN with a lack of non-classical monocyte population. The defects in monocyte plasticity may contribute to disease manifestations in PN and a defective cAMP signalling may be the primary effect of the splicing errors caused by USB1 mutation.
Topics: Male; Child; Humans; Monocytes; Skin Abnormalities; Neutropenia; Cytokines; Receptors, IgG; Phosphoric Diester Hydrolases
PubMed: 37779259
DOI: 10.1111/bjh.19128 -
Clinical, Cosmetic and Investigational... 2023Dermatomyositis is an inflammatory myopathy characterized by typical skin findings. Cutaneous findings of DM include heliotrope eruption, Gottron papules, Gottron sign,...
Dermatomyositis is an inflammatory myopathy characterized by typical skin findings. Cutaneous findings of DM include heliotrope eruption, Gottron papules, Gottron sign, poikiloderma, periorbital edema, facial swelling. The unique cutaneous manifestations of dermatomyositis are often resistant to conventional treatments. Narrowband intense pulsed light is a novel treatment that may reduce vasodilation. Furthermore, it may have a role in regulating inflammation associated with dermatomyositis. We present a case of cutaneous dermatomyositis that was successfully treated with narrowband intense pulsed light.
PubMed: 37719932
DOI: 10.2147/CCID.S426762 -
The Journal of Biological Chemistry Sep 2023The levels of non-coding RNAs (ncRNAs) are regulated by transcription, RNA processing, and RNA degradation pathways. One mechanism for the degradation of ncRNAs involves... (Review)
Review
The levels of non-coding RNAs (ncRNAs) are regulated by transcription, RNA processing, and RNA degradation pathways. One mechanism for the degradation of ncRNAs involves the addition of oligo(A) tails by non-canonical poly(A) polymerases, which then recruit processive sequence-independent 3' to 5' exonucleases for RNA degradation. This pathway of decay is also regulated by three 3' to 5' exoribonucleases, USB1, PARN, and TOE1, which remove oligo(A) tails and thereby can protect ncRNAs from decay in a manner analogous to the deubiquitination of proteins. Loss-of-function mutations in these genes lead to premature degradation of some ncRNAs and lead to specific human diseases such as Poikiloderma with Neutropenia (PN) for USB1, Dyskeratosis Congenita (DC) for PARN and Pontocerebellar Hypoplasia type 7 (PCH7) for TOE1. Herein, we review the biochemical properties of USB1, PARN, and TOE1, how they modulate ncRNA levels, and their roles in human diseases.
Topics: Humans; Dyskeratosis Congenita; Exoribonucleases; Neutropenia; RNA Stability; RNA, Untranslated; Loss of Function Mutation
PubMed: 37544646
DOI: 10.1016/j.jbc.2023.105139 -
Pediatric Dermatology 2024Serine/threonine kinase 4 deficiency (STK4 or MST1, OMIM:614868) is an autosomal recessive (AR) combined immunodeficiency that can present with skin lesions such as...
Serine/threonine kinase 4 deficiency (STK4 or MST1, OMIM:614868) is an autosomal recessive (AR) combined immunodeficiency that can present with skin lesions such as epidermodysplasia verruciformis-like lesions (EVLL). Herein, we describe a 17-year-old male patient born from consanguineous parents presenting with recurrent respiratory infections, verruciform plaques, poikiloderma, chronic benign lymphoproliferation, and Sjögren syndrome with suspected interstitial lymphocytic pneumonia.
Topics: Male; Humans; Adolescent; Epidermodysplasia Verruciformis; Skin Diseases; Papillomaviridae; Primary Immunodeficiency Diseases; Protein Serine-Threonine Kinases; Intracellular Signaling Peptides and Proteins
PubMed: 37515487
DOI: 10.1111/pde.15400