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Lidia Larizza - One of the best experts on this subject based on the ideXlab platform.
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Insights into Mutation Effect in Three Poikiloderma with Neutropenia Patients by Transcript Analysis and Disease Evolution of Reported Patients with the Same Pathogenic Variants
Journal of clinical immunology, 2018Co-Authors: Elisa Colombo, Cristina Gervasini, Nursel Elcioglu, C. Graziano, P. Farinelli, E. Di Fede, I. Neri, E. Facchini, M. Greco, Lidia LarizzaAbstract:Purpose Poikiloderma with neutropenia (PN) is a genodermatosis currently described in 77 patients, all presenting with early-onset Poikiloderma, neutropenia, and several additional signs. Biallelic loss-of-function mutations in USB1 gene are detected in all molecularly tested patients but genotype-phenotype correlation remains elusive. Cancer predisposition is recognized among PN features and pathogenic variants found in patients who developed early in life myelodysplasia (n = 12), acute myeloid leukemia (n = 2), and squamous cell carcinoma (n = 2) should be kept into account in management and follow-up of novel patients. This will hopefully allow achieving data clustered on specific mutations relevant to oncological surveillance of the carrier patients.
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Insights into Mutation Effect in Three Poikiloderma with Neutropenia Patients by Transcript Analysis and Disease Evolution of Reported Patients with the Same Pathogenic Variants
'Springer Science and Business Media LLC', 2018Co-Authors: E.a. Colombo, Nursel Elcioglu, C. Graziano, P. Farinelli, E. Di Fede, I. Neri, E. Facchini, M. Greco, C. Gervasini, Lidia LarizzaAbstract:Poikiloderma with neutropenia (PN) is a genodermatosis currently described in 77 patients, all presenting with early-onset Poikiloderma, neutropenia, and several additional signs. Biallelic loss-of-function mutations in USB1 gene are detected in all molecularly tested patients but genotype-phenotype correlation remains elusive. Cancer predisposition is recognized among PN features and pathogenic variants found in patients who developed early in life myelodysplasia (n\u2009=\u200912), acute myeloid leukemia (n\u2009=\u20092), and squamous cell carcinoma (n\u2009=\u20092) should be kept into account in management and follow-up of novel patients. This will hopefully allow achieving data clustered on specific mutations relevant to oncological surveillance of the carrier patients
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REVIEW Open Access Rothmund-Thomson syndrome
2013Co-Authors: Lidia Larizza, Gaia Roversi, Ludovica VolpiAbstract:Rothmund-Thomson syndrome (RTS) is a genodermatosis presenting with a characteristic facial rash (Poikiloderma) associated with short stature, sparse scalp hair, sparse or absent eyelashes and/or eyebrows, juvenile cataracts, skeletal abnormalities, radial ray defects, premature aging and a predisposition to cancer. The prevalence is unknown but around 300 cases have been reported in the literature so far. The diagnostic hallmark is facial erythema, which spreads to the extremities but spares the trunk, and which manifests itself within the first year and then develops into Poikiloderma. Two clinical subforms of RTS have been defined: RTSI characterised by Poikiloderma, ectodermal dysplasia and juvenile cataracts, and RTSII characterised by Poikiloderma, congenital bone defects and an increased risk of osteosarcoma in childhood and skin cancer later in life. The skeletal abnormalities may be overt (frontal bossing, saddle nose and congenital radial ray defects), and/or subtle (visible only by radiographic analysis). Gastrointestinal, respiratory and haematological signs have been reported in a few patients. RTS is transmitted in an autosomal recessive manner and is genetically heterogeneous: RTSII is caused by homozygous or compound heterozygous mutations in the RECQL4 helicase gene (detected in 60-65 % of RTS patients), whereas the aetiology in RTSI remains unknown. Diagnosis is based on clinical findings (primarily on the age of onset, spreading and appearance of the Poikiloderma) and molecular analysis for RECQL4 mutations. Missense mutations are rare, whil
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Rothmund-Thomson syndrome
Orphanet Journal of Rare Diseases, 2010Co-Authors: Lidia Larizza, Gaia Roversi, Leda VolpiAbstract:Rothmund-Thomson syndrome (RTS) is a genodermatosis presenting with a characteristic facial rash (Poikiloderma) associated with short stature, sparse scalp hair, sparse or absent eyelashes and/or eyebrows, juvenile cataracts, skeletal abnormalities, radial ray defects, premature aging and a predisposition to cancer. The prevalence is unknown but around 300 cases have been reported in the literature so far. The diagnostic hallmark is facial erythema, which spreads to the extremities but spares the trunk, and which manifests itself within the first year and then develops into Poikiloderma. Two clinical subforms of RTS have been defined: RTSI characterised by Poikiloderma, ectodermal dysplasia and juvenile cataracts, and RTSII characterised by Poikiloderma, congenital bone defects and an increased risk of osteosarcoma in childhood and skin cancer later in life. The skeletal abnormalities may be overt (frontal bossing, saddle nose and congenital radial ray defects), and/or subtle (visible only by radiographic analysis). Gastrointestinal, respiratory and haematological signs have been reported in a few patients. RTS is transmitted in an autosomal recessive manner and is genetically heterogeneous: RTSII is caused by homozygous or compound heterozygous mutations in the RECQL4 helicase gene (detected in 60-65% of RTS patients), whereas the aetiology in RTSI remains unknown. Diagnosis is based on clinical findings (primarily on the age of onset, spreading and appearance of the Poikiloderma) and molecular analysis for RECQL4 mutations. Missense mutations are rare, while frameshift, nonsense mutations and splice-site mutations prevail. A fully informative test requires transcript analysis not to overlook intronic deletions causing missplicing. The diagnosis of RTS should be considered in all patients with osteosarcoma, particularly if associated with skin changes. The differential diagnosis should include other causes of childhood Poikiloderma (including dyskeratosis congenita, Kindler syndrome and Poikiloderma with Neutropaenia), other rare genodermatoses with prominent telangiectasias (including Bloom syndrome, Werner syndrome and Ataxia-telangiectasia) and the allelic disorders, RAPADILINO syndrome and Baller-Gerold syndrome, which also share some clinical features. A few mutations recur in all three RECQL4 diseases. Genetic counselling should be provided for RTS patients and their families, together with a recommendation for cancer surveillance for all patients with RTSII. Patients should be managed by a multidisciplinary team and offered long term follow-up. Treatment includes the use of pulsed dye laser photocoagulation to improve the telangiectatic component of the rash, surgical removal of the cataracts and standard treatment for individuals who develop cancer. Although some clinical signs suggest precocious aging, life expectancy is not impaired in RTS patients if they do not develop cancer. Outcomes in patients with osteosarcoma are similar in RTS and non-RTS patients, with a five-year survival rate of 60-70%. The sensitivity of RTS cells to genotoxic agents exploiting cells with a known RECQL4 status is being elucidated and is aimed at optimizing the chemotherapeutic regimen for osteosarcoma.
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Rothmund-Thomson syndrome
Orphanet Journal of Rare Diseases, 2010Co-Authors: Lidia Larizza, Gaia Roversi, Ludovica VolpiAbstract:Rothmund-Thomson syndrome (RTS) is a genodermatosis presenting with a characteristic facial rash (Poikiloderma) associated with short stature, sparse scalp hair, sparse or absent eyelashes and/or eyebrows, juvenile cataracts, skeletal abnormalities, radial ray defects, premature aging and a predisposition to cancer. The prevalence is unknown but around 300 cases have been reported in the literature so far. The diagnostic hallmark is facial erythema, which spreads to the extremities but spares the trunk, and which manifests itself within the first year and then develops into Poikiloderma. Two clinical subforms of RTS have been defined: RTSI characterised by Poikiloderma, ectodermal dysplasia and juvenile cataracts, and RTSII characterised by Poikiloderma, congenital bone defects and an increased risk of osteosarcoma in childhood and skin cancer later in life. The skeletal abnormalities may be overt (frontal bossing, saddle nose and congenital radial ray defects), and/or subtle (visible only by radiographic analysis). Gastrointestinal, respiratory and haematological signs have been reported in a few patients. RTS is transmitted in an autosomal recessive manner and is genetically heterogeneous: RTSII is caused by homozygous or compound heterozygous mutations in the RECQL4 helicase gene (detected in 60-65% of RTS patients), whereas the aetiology in RTSI remains unknown. Diagnosis is based on clinical findings (primarily on the age of onset, spreading and appearance of the Poikiloderma) and molecular analysis for RECQL4 mutations. Missense mutations are rare, while frameshift, nonsense mutations and splice-site mutations prevail. A fully informative test requires transcript analysis not to overlook intronic deletions causing missplicing. The diagnosis of RTS should be considered in all patients with osteosarcoma, particularly if associated with skin changes. The differential diagnosis should include other causes of childhood Poikiloderma (including dyskeratosis congenita, Kindler syndrome and Poikiloderma with Neutropaenia), other rare genodermatoses with prominent telangiectasias (including Bloom syndrome, Werner syndrome and Ataxia-telangiectasia) and the allelic disorders, RAPADILINO syndrome and Baller-Gerold syndrome, which also share some clinical features. A few mutations recur in all three RECQL4 diseases. Genetic counselling should be provided for RTS patients and their families, together with a recommendation for cancer surveillance for all patients with RTSII. Patients should be managed by a multidisciplinary team and offered long term follow-up. Treatment includes the use of pulsed dye laser photocoagulation to improve the telangiectatic component of the rash, surgical removal of the cataracts and standard treatment for individuals who develop cancer. Although some clinical signs suggest precocious aging, life expectancy is not impaired in RTS patients if they do not develop cancer. Outcomes in patients with osteosarcoma are similar in RTS and non-RTS patients, with a five-year survival rate of 60-70%. The sensitivity of RTS cells to genotoxic agents exploiting cells with a known RECQL4 status is being elucidated and is aimed at optimizing the chemotherapeutic regimen for osteosarcoma.
Ljubka Miteva - One of the best experts on this subject based on the ideXlab platform.
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Subacute cutaneous lupus erythematosus presenting with generalized Poikiloderma
Journal of The American Academy of Dermatology, 2000Co-Authors: K. Pramatarov, Snejina Vassileva, Ljubka MitevaAbstract:Abstract A 64-year-old woman experienced progressive generalized Poikiloderma after an episode of sunburn 4 years earlier. The diagnosis of subacute cutaneous lupus erythematosus (SCLE) was confirmed by the presence of anti-Ro/SS-A and antinuclear antibodies, the histology, and the direct immunofluorescent findings (ie, positive lupus band test and "dustlike" epidermal IgG staining pattern). Poikiloderma has not been previously reported in the spectrum of SCLE. As a major pathomechanism of SCLE, photosensitivity might explain this uncommon clinical manifestation of the disease. (J Am Acad Dermatol 2000;42:286-8.)
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Subacute cutaneous lupus erythematosus presenting with generalized Poikiloderma.
Journal of the American Academy of Dermatology, 2000Co-Authors: K. Pramatarov, Snejina Vassileva, Ljubka MitevaAbstract:A 64-year-old woman experienced progressive generalized Poikiloderma after an episode of sunburn 4 years earlier. The diagnosis of subacute cutaneous lupus erythematosus (SCLE) was confirmed by the presence of anti-Ro/SS-A and antinuclear antibodies, the histology, and the direct immunofluorescent findings (ie, positive lupus band test and "dust-like" epidermal IgG staining pattern). Poikiloderma has not been previously reported in the spectrum of SCLE. As a major pathomechanism of SCLE, photosensitivity might explain this uncommon clinical manifestation of the disease.
C. Baumann - One of the best experts on this subject based on the ideXlab platform.
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Search for ReCQL4 mutations in 39 patients genotyped for suspected Rothmund-Thomson/Baller-Gerold syndromes
Clinical Genetics, 2015Co-Authors: J. Piard, B. Aral, P. Vabres, M. Holder-espinasse, André Mégarbané, S. Gauthier, V. Capra, G. Pierquin, P. Callier, C. BaumannAbstract:Three overlapping conditions, namely Rothmund-Thomson (RTS), Baller-Gerold (BGS) and RAPADILINO syndromes, have been attributed to RECQL4 mutations. Differential diagnoses depend on the clinical presentation, but the numbers of known genes remain low, leading to the widespread prescription of RECQL4 sequencing. The aim of our study was therefore to determine the best clinical indicators for the presence of RECQL4 mutations in a series of 39 patients referred for RECQL4 molecular analysis and belonging to the RTS (27 cases) and BGS (12 cases) spectrum. One or two deleterious RECQL4 mutations were found in 10/27 patients referred for RTS diagnosis. Clinical and molecular reevaluation led to a different diagnosis in 7/17 negative cases, including Clericuzio-type Poikiloderma with neutropenia, hereditary sclerosing Poikiloderma, and craniosynostosis/anal anomalies/porokeratosis. No RECQL4 mutations were found in the BGS group without Poikiloderma, confirming that RECQL4 sequencing was not indicated in this phenotype. One chromosomal abnormality and one TWIST mutation was found in this cohort. This study highlights the search for differential diagnoses before the prescription of RECQL4 sequencing in this clinically heterogeneous group. The combination of clinically defined subgroups and next-generation sequencing will hopefully bring to light new molecular bases of syndromes with Poikiloderma, as well as BGS without Poikiloderma.
K. Pramatarov - One of the best experts on this subject based on the ideXlab platform.
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Subacute cutaneous lupus erythematosus presenting with generalized Poikiloderma
Journal of The American Academy of Dermatology, 2000Co-Authors: K. Pramatarov, Snejina Vassileva, Ljubka MitevaAbstract:Abstract A 64-year-old woman experienced progressive generalized Poikiloderma after an episode of sunburn 4 years earlier. The diagnosis of subacute cutaneous lupus erythematosus (SCLE) was confirmed by the presence of anti-Ro/SS-A and antinuclear antibodies, the histology, and the direct immunofluorescent findings (ie, positive lupus band test and "dustlike" epidermal IgG staining pattern). Poikiloderma has not been previously reported in the spectrum of SCLE. As a major pathomechanism of SCLE, photosensitivity might explain this uncommon clinical manifestation of the disease. (J Am Acad Dermatol 2000;42:286-8.)
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Subacute cutaneous lupus erythematosus presenting with generalized Poikiloderma.
Journal of the American Academy of Dermatology, 2000Co-Authors: K. Pramatarov, Snejina Vassileva, Ljubka MitevaAbstract:A 64-year-old woman experienced progressive generalized Poikiloderma after an episode of sunburn 4 years earlier. The diagnosis of subacute cutaneous lupus erythematosus (SCLE) was confirmed by the presence of anti-Ro/SS-A and antinuclear antibodies, the histology, and the direct immunofluorescent findings (ie, positive lupus band test and "dust-like" epidermal IgG staining pattern). Poikiloderma has not been previously reported in the spectrum of SCLE. As a major pathomechanism of SCLE, photosensitivity might explain this uncommon clinical manifestation of the disease.
Sandra Mercier - One of the best experts on this subject based on the ideXlab platform.
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Expanding the clinical spectrum of hereditary fibrosing Poikiloderma with tendon contractures, myopathy and pulmonary fibrosis due to FAM111B mutations
Orphanet Journal of Rare Diseases, 2015Co-Authors: Sandra Mercier, N. Bodak, Sebastien Kury, Thomas Besnard, Emmanuelle Salort-campana, Armelle Magot, Uchenna Agbim, Chantal Bou-hanna, Flora Bréhéret, Perrine BrunelleAbstract:Background Hereditary Fibrosing Poikiloderma (HFP) with tendon contractures, myopathy and pulmonary fibrosis (POIKTMP [MIM 615704]) is a very recently described entity of syndromic inherited Poikiloderma. Previously by using whole exome sequencing in five families, we identified the causative gene, FAM111B (NM_198947.3), the function of which is still unknown. Our objective in this study was to better define the specific features of POIKTMP through a larger series of patients. Methods Clinical and molecular data of two families and eight independent sporadic cases, including six new cases, were collected. Results Key features consist of: (i) early-onset Poikiloderma, hypotrichosis and hypohidrosis; (ii) multiple contractures, in particular triceps surae muscle contractures; (iii) diffuse progressive muscular weakness; (iv) pulmonary fibrosis in adulthood and (v) other features including exocrine pancreatic insufficiency, liver impairment and growth retardation. Muscle magnetic resonance imaging was informative and showed muscle atrophy and fatty infiltration. Histological examination of skeletal muscle revealed extensive fibroadipose tissue infiltration. Microscopy of the skin showed a scleroderma-like aspect with fibrosis and alterations of the elastic network. FAM111B gene analysis identified five different missense variants (two recurrent mutations were found respectively in three and four independent families). All the mutations were predicted to localize in the trypsin-like cysteine/serine peptidase domain of the protein. We suggest gain-of-function or dominant-negative mutations resulting in FAM111B enzymatic activity changes. Conclusions HFP with tendon contractures, myopathy and pulmonary fibrosis, is a multisystemic disorder due to autosomal dominant FAM111B mutations. Future functional studies will help in understanding the specific pathological process of this fibrosing disorder.
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expanding the clinical spectrum of hereditary fibrosing Poikiloderma with tendon contractures myopathy and pulmonary fibrosis due to fam111b mutations
Orphanet Journal of Rare Diseases, 2015Co-Authors: Sandra Mercier, N. Bodak, Sebastien Kury, Chantal Bouhanna, Thomas Besnard, Armelle Magot, Uchenna Agbim, Flora Bréhéret, Emmanuelle Salortcampana, Perrine BrunelleAbstract:Hereditary Fibrosing Poikiloderma (HFP) with tendon contractures, myopathy and pulmonary fibrosis (POIKTMP [MIM 615704]) is a very recently described entity of syndromic inherited Poikiloderma. Previously by using whole exome sequencing in five families, we identified the causative gene, FAM111B (NM_198947.3), the function of which is still unknown. Our objective in this study was to better define the specific features of POIKTMP through a larger series of patients. Clinical and molecular data of two families and eight independent sporadic cases, including six new cases, were collected. Key features consist of: (i) early-onset Poikiloderma, hypotrichosis and hypohidrosis; (ii) multiple contractures, in particular triceps surae muscle contractures; (iii) diffuse progressive muscular weakness; (iv) pulmonary fibrosis in adulthood and (v) other features including exocrine pancreatic insufficiency, liver impairment and growth retardation. Muscle magnetic resonance imaging was informative and showed muscle atrophy and fatty infiltration. Histological examination of skeletal muscle revealed extensive fibroadipose tissue infiltration. Microscopy of the skin showed a scleroderma-like aspect with fibrosis and alterations of the elastic network. FAM111B gene analysis identified five different missense variants (two recurrent mutations were found respectively in three and four independent families). All the mutations were predicted to localize in the trypsin-like cysteine/serine peptidase domain of the protein. We suggest gain-of-function or dominant-negative mutations resulting in FAM111B enzymatic activity changes. HFP with tendon contractures, myopathy and pulmonary fibrosis, is a multisystemic disorder due to autosomal dominant FAM111B mutations. Future functional studies will help in understanding the specific pathological process of this fibrosing disorder.
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CUGC for hereditary fibrosing Poikiloderma with tendon contractures, myopathy, and pulmonary fibrosis (POIKTMP).
European journal of human genetics : EJHG, 2015Co-Authors: Sebastien Kury, Sandra Mercier, Gasnat Shaboodien, Nonhlanhla P Khumalo, Thomas Besnard, Sébastien Barbarot, Bongani M. Mayosi, Stéphane BézieauAbstract:CUGC for hereditary fibrosing Poikiloderma with tendon contractures, myopathy, and pulmonary fibrosis (POIKTMP)
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mutations in fam111b cause hereditary fibrosing Poikiloderma with tendon contracture myopathy and pulmonary fibrosis
American Journal of Human Genetics, 2013Co-Authors: Sandra Mercier, N. Bodak, Sebastien Kury, Gasnat Shaboodien, Darren T Houniet, Nonhlanhla P Khumalo, Chantal Bouhanna, Valerie Cormierdaire, Albert David, Laurence FaivreAbstract:Congenital Poikiloderma is characterized by a combination of mottled pigmentation, telangiectasia, and epidermal atrophy in the first few months of life. We have previously described a South African European-descent family affected by a rare autosomal-dominant form of hereditary fibrosing Poikiloderma accompanied by tendon contracture, myopathy, and pulmonary fibrosis. Here, we report the identification of causative mutations in FAM111B by whole-exome sequencing. In total, three FAM111B missense mutations were identified in five kindreds of different ethnic backgrounds. The mutation segregated with the disease in one large pedigree, and mutations were de novo in two other pedigrees. All three mutations were absent from public databases and were not observed on Sanger sequencing of 388 ethnically matched control subjects. The three single-nucleotide mutations code for amino acid changes that are clustered within a putative trypsin-like cysteine/serine peptidase domain of FAM111B. These findings provide evidence of the involvement of FAM111B in congenital Poikiloderma and multisystem fibrosis.
