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Analysis of short stature homeobox-containing gene ( SHOX) and auxological phenotype in dyschondrosteosis and isolated Madelung deformity

Grigelioniene, Giedre; Schoumans, Jacqueline; Neumeyer, Lo; Ivarsson, Sten LU ; Eklof, Ole; Enkvist, Ove; Tordai, Paul; Fosdal, Inger; Myhre, Anne and Westphal, Otto, et al. (2001) In Human Genetics 109(5). p.551-558
Abstract
Dyschondrosteosis (DCO; also called Leri-Weill syndrome) is a skeletal dysplasia characterised by disproportionate short stature because of mesomelic shortening of the limbs. Madelung deformity is a feature of DCO that is distinctive, variable in expressivity and frequently observed. Mutations of the SHOX (short stature homeobox-containing) gene have been previously described as causative in DCO. Isolated Madelung deformity (IMD) without the clinical characteristics of DCO has also been described in sporadic and a few familial cases but the genetic defect underlying IMD is unknown. In this study, we have examined 28 probands with DCO and seven probands with IMD for mutations in the SHOX gene by using polymorphic CA-repeat analysis,... (More)
Dyschondrosteosis (DCO; also called Leri-Weill syndrome) is a skeletal dysplasia characterised by disproportionate short stature because of mesomelic shortening of the limbs. Madelung deformity is a feature of DCO that is distinctive, variable in expressivity and frequently observed. Mutations of the SHOX (short stature homeobox-containing) gene have been previously described as causative in DCO. Isolated Madelung deformity (IMD) without the clinical characteristics of DCO has also been described in sporadic and a few familial cases but the genetic defect underlying IMD is unknown. In this study, we have examined 28 probands with DCO and seven probands with IMD for mutations in the SHOX gene by using polymorphic CA-repeat analysis, fluorescence in situ hybridisation (FISH), Southern blotting, direct sequencing and fibre-FISH analyses. This was combined with auxological examination of the probands and their family members. Evaluation of the auxological data showed a wide intra- and interfamilial phenotype variability in DCO. Out of 28 DCO probands, 22 (79%) were shown to have mutations in the SHOX gene. Sixteen unrelated DCO families had SHOX gene deletions. Four novel DCO-associated mutations were found in different families. In two additional DCO families, the previously described nonsense mutation (Arg195Stop) was detected. We conclude that mutations in the SHOX gene are the major factor in the pathogenesis of DCO. In a female proband with severe IMD and her unaffected sister, we detected an intrachromosomal duplication of the SHOX gene. (Less)
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Human Genetics
volume
109
issue
5
pages
551 - 558
publisher
Springer
external identifiers
  • pmid:11735031
  • scopus:0035177711
ISSN
1432-1203
DOI
10.1007/s00439-001-0609-y
language
English
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yes
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dcfaa3af-c554-490e-b857-08542d57f037 (old id 1121276)
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2008-06-30 09:35:44
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2018-05-29 11:54:21
@article{dcfaa3af-c554-490e-b857-08542d57f037,
  abstract     = {Dyschondrosteosis (DCO; also called Leri-Weill syndrome) is a skeletal dysplasia characterised by disproportionate short stature because of mesomelic shortening of the limbs. Madelung deformity is a feature of DCO that is distinctive, variable in expressivity and frequently observed. Mutations of the SHOX (short stature homeobox-containing) gene have been previously described as causative in DCO. Isolated Madelung deformity (IMD) without the clinical characteristics of DCO has also been described in sporadic and a few familial cases but the genetic defect underlying IMD is unknown. In this study, we have examined 28 probands with DCO and seven probands with IMD for mutations in the SHOX gene by using polymorphic CA-repeat analysis, fluorescence in situ hybridisation (FISH), Southern blotting, direct sequencing and fibre-FISH analyses. This was combined with auxological examination of the probands and their family members. Evaluation of the auxological data showed a wide intra- and interfamilial phenotype variability in DCO. Out of 28 DCO probands, 22 (79%) were shown to have mutations in the SHOX gene. Sixteen unrelated DCO families had SHOX gene deletions. Four novel DCO-associated mutations were found in different families. In two additional DCO families, the previously described nonsense mutation (Arg195Stop) was detected. We conclude that mutations in the SHOX gene are the major factor in the pathogenesis of DCO. In a female proband with severe IMD and her unaffected sister, we detected an intrachromosomal duplication of the SHOX gene.},
  author       = {Grigelioniene, Giedre and Schoumans, Jacqueline and Neumeyer, Lo and Ivarsson, Sten and Eklof, Ole and Enkvist, Ove and Tordai, Paul and Fosdal, Inger and Myhre, Anne and Westphal, Otto and Nilsson, Nils and Elfving, Maria and Ellis, Ian and Anderlid, Britt-Marie and Fransson, Ingegerd and Tapia-Paez, Isabel and Nordenskjold, Magnus and Hagenas, Lars and Dumanski, Jan P.},
  issn         = {1432-1203},
  language     = {eng},
  number       = {5},
  pages        = {551--558},
  publisher    = {Springer},
  series       = {Human Genetics},
  title        = {Analysis of short stature homeobox-containing gene ( SHOX) and auxological phenotype in dyschondrosteosis and isolated Madelung deformity},
  url          = {http://dx.doi.org/10.1007/s00439-001-0609-y},
  volume       = {109},
  year         = {2001},
}