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

Dyschondrosteosis (DCO; also called Léri-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 th...

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Bibliographic Details
Published in:	Human genetics Vol. 109; no. 5; pp. 551 - 558
Main Authors:	GRIGELIONIENE, Giedre, SCHOUMANS, Jacqueline, NILSSON, Nils Östen, ELFVING, Maria, ELLIS, Ian, ANDERLID, Britt-Marie, FRANSSON, Ingegerd, TAPIA-PAEZ, Isabel, NORDENSKJÖLD, Magnus, HAGENÄS, Lars, DUMANSKI, Jan P, NEUMEYER, Lo, IVARSSON, Sten Anders, EKLÖF, Ole, ENKVIST, Ove, TORDAI, Paul, FOSDAL, Inger, MYHRE, Anne Grethe, WESTPHAL, Otto
Format:	Journal Article
Language:	English
Published:	Heidelberg Springer 01-11-2001 Berlin New York, NY
Subjects:	Basic Medicine Biological and medical sciences Blotting, Southern Body Height - genetics Fundamental and applied biological sciences. Psychology Genes, Homeobox Homeodomain Proteins - genetics Humans In Situ Hybridization, Fluorescence Medical and Health Sciences Medical Genetics Medicin och hälsovetenskap Medicinsk genetik Medicinska och farmaceutiska grundvetenskaper Molecular and cellular biology Osteochondrodysplasias - genetics Phenotype Polymerase Chain Reaction Short Stature Homeobox Protein Syndrome
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Summary:	Dyschondrosteosis (DCO; also called Léri-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.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2
ISSN:	0340-6717 1432-1203 1432-1203
DOI:	10.1007/s00439-001-0609-y