The Experts below are selected from a list of 21 Experts worldwide ranked by ideXlab platform
Steve Jeffery - One of the best experts on this subject based on the ideXlab platform.
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Primary non-syndromic lymphoedema (Meige Disease) is not caused by mutations in FOXC2
European Journal of Human Genetics, 2008Co-Authors: Tayebeh Rezaie, Rose Ghoroghchian, Rachel Bell, Glen Brice, Ali Hasan, Kevin Burnand, Steve Vernon, Sahar Mansour, Peter Mortimer, Steve JefferyAbstract:Primary lymphoedema is a genetic disorder with numerous phenotypic subgroups. The most common form is the non-syndromic Meige Disease, which is primarily of pubertal or later onset, with oedema clinically indistinguishable from that found in the lymphoedema–distichiasis syndrome. There are also other very rare forms of lymphoedema such as yellow nail syndrome and lymphoedema with ptosis, which are clinically similar to Meige Disease. The only causative genes so far identified for the non-congenital primary lymphoedemas are the transcription factor FOXC2 , where mutations are known to produce lymphoedema with distichiasis, and SOX18 in the very rare condition hypotrichosis–lymphoedema–telangiectasia. This study has examined FOXC2 gene by sequence analysis in 23 affected individuals with Meige Disease. A novel truncating mutation (c.563–584del) was identified in one family and found to segregate with the Disease in eight affected relatives over three generations. This deletion creates a frameshift that predicts a premature stop at nucleotide 599 and truncating the normal protein by 38%. Although the affected patient initially selected for mutation screening from this family had lymphoedema without distichiasis, all but one of his affected relatives who carried the FOXC2 mutation did have accessory eyelashes originating from their meibomian glands. This is further confirmation that of the primary lymphoedemas, only lymphoedema with distichiasis is caused by FOXC2 mutations. All forms of post-pubertal lymphoedema need careful phenotyping for distichiasis, which may prove difficult to confirm unless several family members are examined, and cannot ever be assumed to be absent from self-report.
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Identification of eight novel VEGFR-3 mutations in families with primary congenital lymphoedema
Journal of medical genetics, 2003Co-Authors: A L Evans, Steve Jeffery, R Bell, G Brice, P Mortimer, P Comeglio, C Lipede, Mansoor Sarfarazi, A H ChildAbstract:Primary lymphoedema is oedema that occurs as a consequence of a failure of lymph drainage and arises from an intrinsic abnormality of the lymphatic system.1 Familial lymphoedema usually segregates as an autosomal dominant trait with reported variable expression and reduced penetrance.2,3 Primary lymphoedema can be classified according to age of onset, at birth as primary congenital lymphoedema (PCL) or Milroy Disease (MIM 153100) or, more commonly, after puberty as Meige Disease (MIM 153200). Lymphoedema may occur as part of a well recognised syndrome, where the genetic defect may or may not be known, for example in Turner or Noonan syndrome (MIM 163950).4 Lymphoedema can also occur in association with other clinical features—for example, pubertal onset autosomal dominant lymphoedema with distichiasis (LD; MIM 153400), which has been linked to 16q24.3.5,6 The gene for LD has recently been identified as FOXC2 ( MFH-1 ) (MIM 602402), a member of the forkhead/winged-helix family of transcription factors, and mutations within this gene have been identified in families with LD.7–10 We have previously reported linkage to 5q35.3 in one large American family and four British families with PCL.3 This has also been shown independently by two other groups.11,12 Subsequent mutations were reported in the gene encoding the vascular endothelial growth factor receptor 3 ( VEGFR-3 , also known as FLT4 ; MIM 136352; GenBank X68203 and S66407), which resulted in defective VEGFR-3 tyrosine kinase activity and signalling, suggesting this was the cause of primary lymphoedema.12,,13 The VEGFR-3 gene is expressed in the lymphatic endothelium of adult tissues.14 Targeted disruption of Vegfr-3 in mice leads to embryonic death at day 9.5 owing to defective development of large blood vessels and cardiovascular failure.15 Moreover, cutaneous overexpression of its ligand, vascular endothelial growth factor C …
John J.e. Mulvihill - One of the best experts on this subject based on the ideXlab platform.
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lymphangiosarcoma in late onset hereditary lymphedema case report and nosological implications
American Journal of Medical Genetics, 1995Co-Authors: C Hans M D Andersson, John J.e. Mulvihill, Dilys M ParryAbstract:Hereditary lymphedemas that are not associated with other malformations usually affect the lower limbs and are inherited in an autosomal dominant fashion. These non-syndromic hereditary lymphedemas are categorized by their age of onset, being either congenital (Milroy Disease) or having an onset in childhood or around puberty (Meige Disease). We describe a family in which three individuals in three generations had unusually late onset of lym-phedema in their mid-twenties or thirties. The proband additionally developed a very rare lymphangiosarcoma. This tumor, usually associated with post-mastectomy lym-phedema, has not been described in late-onset hereditary lymphedema. Because of an unusually high incidence of multiple primary tumors in association with lymphangiosarcoma in the literature (approximately 10%) and the proband's own familial cancer background, we speculate that an inherited predisposition to malignancy may underlie the development of lymphedema-associated lymphangiosarcoma. © 1995 Wiley-Liss, Inc.
C Hans M D Andersson - One of the best experts on this subject based on the ideXlab platform.
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lymphangiosarcoma in late onset hereditary lymphedema case report and nosological implications
American Journal of Medical Genetics, 1995Co-Authors: C Hans M D Andersson, John J.e. Mulvihill, Dilys M ParryAbstract:Hereditary lymphedemas that are not associated with other malformations usually affect the lower limbs and are inherited in an autosomal dominant fashion. These non-syndromic hereditary lymphedemas are categorized by their age of onset, being either congenital (Milroy Disease) or having an onset in childhood or around puberty (Meige Disease). We describe a family in which three individuals in three generations had unusually late onset of lym-phedema in their mid-twenties or thirties. The proband additionally developed a very rare lymphangiosarcoma. This tumor, usually associated with post-mastectomy lym-phedema, has not been described in late-onset hereditary lymphedema. Because of an unusually high incidence of multiple primary tumors in association with lymphangiosarcoma in the literature (approximately 10%) and the proband's own familial cancer background, we speculate that an inherited predisposition to malignancy may underlie the development of lymphedema-associated lymphangiosarcoma. © 1995 Wiley-Liss, Inc.
Kevin Burnand - One of the best experts on this subject based on the ideXlab platform.
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Primary non-syndromic lymphoedema (Meige Disease) is not caused by mutations in FOXC2
European Journal of Human Genetics, 2008Co-Authors: Tayebeh Rezaie, Rose Ghoroghchian, Rachel Bell, Glen Brice, Ali Hasan, Kevin Burnand, Steve Vernon, Sahar Mansour, Peter Mortimer, Steve JefferyAbstract:Primary lymphoedema is a genetic disorder with numerous phenotypic subgroups. The most common form is the non-syndromic Meige Disease, which is primarily of pubertal or later onset, with oedema clinically indistinguishable from that found in the lymphoedema–distichiasis syndrome. There are also other very rare forms of lymphoedema such as yellow nail syndrome and lymphoedema with ptosis, which are clinically similar to Meige Disease. The only causative genes so far identified for the non-congenital primary lymphoedemas are the transcription factor FOXC2 , where mutations are known to produce lymphoedema with distichiasis, and SOX18 in the very rare condition hypotrichosis–lymphoedema–telangiectasia. This study has examined FOXC2 gene by sequence analysis in 23 affected individuals with Meige Disease. A novel truncating mutation (c.563–584del) was identified in one family and found to segregate with the Disease in eight affected relatives over three generations. This deletion creates a frameshift that predicts a premature stop at nucleotide 599 and truncating the normal protein by 38%. Although the affected patient initially selected for mutation screening from this family had lymphoedema without distichiasis, all but one of his affected relatives who carried the FOXC2 mutation did have accessory eyelashes originating from their meibomian glands. This is further confirmation that of the primary lymphoedemas, only lymphoedema with distichiasis is caused by FOXC2 mutations. All forms of post-pubertal lymphoedema need careful phenotyping for distichiasis, which may prove difficult to confirm unless several family members are examined, and cannot ever be assumed to be absent from self-report.
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Reduction of the genetic interval for lymphoedema-distichiasis to below 2 Mb
Journal of medical genetics, 2000Co-Authors: R Bell, Sahar Mansour, G Brice, A H Child, Victoria Murday, C. J. Sandy, J R O Collin, P Mortimer, David F. Callen, Kevin BurnandAbstract:Editor—Primary lymphoedema (MIM 153200) is a chronic tissue swelling, most frequently of the lower limbs, which occurs as a consequence of a failure of lymph drainage.1 It arises from an intrinsic abnormality of the lymphatic system and generally shows an autosomal dominant pattern of inheritance with reduced penetrance, variable expression, and variable age of onset.2 There is a strong genetic input into primary lymphoedema, with 35% of all patients showing a positive family history.3 4 The swelling can be present at birth, as in Milroy Disease, but more commonly it becomes clinically apparent during puberty, which is known as Meige Disease.5-7 A variant of pubertal onset lymphoedema is lymphoedema-distichiasis (LD) (MIM 153400). This syndrome is a rare form of primary lymphoedema which is associated with distichiasis, a congenital anomaly in which aberrant eyelashes arise inappropriately from the site of the meibomian gland openings.4 8 The Disease shows an autosomal dominant …
Tayebeh Rezaie - One of the best experts on this subject based on the ideXlab platform.
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Primary non-syndromic lymphoedema (Meige Disease) is not caused by mutations in FOXC2
European Journal of Human Genetics, 2008Co-Authors: Tayebeh Rezaie, Rose Ghoroghchian, Rachel Bell, Glen Brice, Ali Hasan, Kevin Burnand, Steve Vernon, Sahar Mansour, Peter Mortimer, Steve JefferyAbstract:Primary lymphoedema is a genetic disorder with numerous phenotypic subgroups. The most common form is the non-syndromic Meige Disease, which is primarily of pubertal or later onset, with oedema clinically indistinguishable from that found in the lymphoedema–distichiasis syndrome. There are also other very rare forms of lymphoedema such as yellow nail syndrome and lymphoedema with ptosis, which are clinically similar to Meige Disease. The only causative genes so far identified for the non-congenital primary lymphoedemas are the transcription factor FOXC2 , where mutations are known to produce lymphoedema with distichiasis, and SOX18 in the very rare condition hypotrichosis–lymphoedema–telangiectasia. This study has examined FOXC2 gene by sequence analysis in 23 affected individuals with Meige Disease. A novel truncating mutation (c.563–584del) was identified in one family and found to segregate with the Disease in eight affected relatives over three generations. This deletion creates a frameshift that predicts a premature stop at nucleotide 599 and truncating the normal protein by 38%. Although the affected patient initially selected for mutation screening from this family had lymphoedema without distichiasis, all but one of his affected relatives who carried the FOXC2 mutation did have accessory eyelashes originating from their meibomian glands. This is further confirmation that of the primary lymphoedemas, only lymphoedema with distichiasis is caused by FOXC2 mutations. All forms of post-pubertal lymphoedema need careful phenotyping for distichiasis, which may prove difficult to confirm unless several family members are examined, and cannot ever be assumed to be absent from self-report.