+1 Recommend
1 collections
      • Record: found
      • Abstract: found
      • Article: found

      Unique Deletion in Exon 5 of SHOX Gene in a Patient with Idiopathic Short Stature

      Read this article at

          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.


          Background/Aim: It is known that haploinsufficiency for the SHOX gene (short-stature homeobox gene on the X chromosome) is responsible for short stature in Turner syndrome and Leri-Weill dyschondrogenesis, and it has been reported that it is responsible for upwards of 1 in 50 cases of idiopathic short stature. SHOX haploinsufficiency is also associated with various radiographic abnormalities, such as coarse trabecular pattern, short metacarpals/metatarsals with metaphyseal flaring, altered osseous alignment at the wrist, radial/tibial bowing, triangularization of the radial head, abnormal tuberosity of the humerus, and an abnormal femoral neck. Shortening and bowing of the radius and dorsal dislocation of the distal ulna characterize the Madelung deformity. These characteristic findings led us to do a study assessing the predictive value of certain radiographic features in association with genetic markers of idiopathic short stature. Methods: Here we describe a case of a Hispanic male with idiopathic short stature and Madelung deformity with a novel mutation in the SHOX gene. Results: Additional studies revealed a strong family history of short stature and the same SHOX mutation segregating from the mother. Conclusion: This case resulted in the description of a novel mutation in exon 5 (M202delA) and suggests the importance of screening for SHOX mutations in patients with idiopathic short stature with subtle radiographic abnormalities, including the components of the Madelung deformity in their bone age films.

          Related collections

          Most cited references 15

          • Record: found
          • Abstract: found
          • Article: not found

          Mutation and deletion of the pseudoautosomal gene SHOX cause Leri-Weill dyschondrosteosis.

          Leri-Weill Dyschondrosteosis (LWD; OMIM 127300) is a dominantly inherited skeletal dysplasia characterized by disproportionate short stature with predominantly mesomelic limb shortening. Expression is variable and consistently more severe in females, who frequently display the Madelung deformity of the forearm (shortening and bowing of the radius with dorsal subluxation of the distal ulna). The rare Langer Mesomelic Dysplasia (LD; OMIM 249700), characterized by severe short stature with hypoplasia/aplasia of the ulna and fibula, has been postulated to be the homozygous form of LWD (refs 4-6). In a six-generation pedigree with LWD, we established linkage to the marker DXYS6814 in the pseudoautosomal region (PAR1) of the X and Y chromosomes (Z max=6.28; theta=0). Linkage analysis of three smaller pedigrees increased the lod score to 8.68 (theta=0). We identified submicroscopic PAR1 deletions encompassing the recently described short stature homeobox-containing gene SHOX (refs 7,8) segregating with the LWD phenotype in 5 families. A point mutation leading to a premature stop in exon 4 of SHOX was identified in one LWD family.
            • Record: found
            • Abstract: found
            • Article: not found

            SHOX mutations in dyschondrosteosis (Leri-Weill syndrome).

            Dyschondrosteosis (DCS) is an autosomal dominant form of mesomelic dysplasia with deformity of the forearm (Madelung deformity; ref. 3). Based on the observation of XY translocations (p22,q12; refs 4-6) in DCS patients, we tested the pseudoautosomal region in eight families with DCS and showed linkage of the DCS gene to a microsatellite DNA marker at the DXYS233 locus (Zmax=6.26 at theta=0). The short stature homeobox-containing gene (SHOX), involved in idiopathic growth retardation and possibly Turner short stature, maps to this region and was therefore regarded as a strong candidate gene in DCS. Here, we report large-scale deletions (in seven families) and a nonsense mutation (in one family) of SHOX in patients with DCS and show that Langer mesomelic dwarfism results from homozygous mutations at the DCS locus.
              • Record: found
              • Abstract: found
              • Article: not found

              Effect of growth hormone treatment on adult height of children with idiopathic short stature. Genentech Collaborative Group.

              Short-term administration of growth hormone to children with idiopathic short stature results in increases in growth rate and standard-deviation scores for height. However, the effect of long-term growth hormone therapy on adult height in these children is unknown. We studied 121 children with idiopathic short stature, all of whom had an initial height below the third percentile, low growth rates, and maximal stimulated serum concentrations of growth hormone of at least 10 microg per liter. The children were treated with growth hormone (0.3 mg per kilogram of body weight per week) for 2 to 10 years. Eighty of these children have reached adult height, with a bone age of at least 16 years in the boys and at least 14 years in the girls, and pubertal stage 4 or 5. The difference between the predicted adult height before treatment and achieved adult height was compared with the corresponding difference in three untreated normal or short-statured control groups. In the 80 children who have reached adult height, growth hormone treatment increased the mean standard-deviation score for height (number of standard deviations from the mean height for chronologic age) from -2.7 to -1.4. The mean (+/-SD) difference between predicted adult height before treatment and achieved adult height was +5.0+/-5.1 cm for boys and +5.9+/-5.2 cm for girls. The difference between predicted and achieved adult height among treated boys was 9.2 cm greater than the corresponding difference among untreated boys with initial standard-deviation scores of less than -2, and the difference among treated girls was 5.7 cm greater than the difference among untreated girls. Long-term administration of growth hormone to children with idiopathic short stature can increase adult height to a level above the predicted adult height and above the adult height of untreated historical control children.

                Author and article information

                Horm Res Paediatr
                Hormone Research in Paediatrics
                S. Karger AG
                February 2007
                06 October 2006
                : 67
                : 2
                : 61-66
                aCenter for Craniofacial Disorders and bDivision of Pediatric Endocrinology, Children’s Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, N.Y., USA
                96087 Horm Res 2007;67:61–66
                © 2007 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                Page count
                Figures: 3, References: 21, Pages: 6
                Novel Insights from Clinical Practice


                Comment on this article