The Experts below are selected from a list of 846 Experts worldwide ranked by ideXlab platform
Judith L. Ross - One of the best experts on this subject based on the ideXlab platform.
-
Clinical and Molecular Evaluation of SHOX/PAR1 Duplications in Léri-Weill Dyschondrosteosis (LWD) and Idiopathic Short Stature (ISS)
The Journal of Clinical Endocrinology & Metabolism, 2011Co-Authors: Sara Benito-sanz, Eva Barroso, Damian Heine-suñer, Alfonso Hisado-oliva, Valeria Romanelli, Jordi Rosell, A. Aragones, María Caimari, Jesús Argente, Judith L. RossAbstract:We report on the largest collection of SHOX duplications detected to date and discuss their potential association with Leri-Weill Dyschondrosteosis and idiopathic short stature.
-
clinical and molecular evaluation of shox par1 duplications in leri weill Dyschondrosteosis lwd and idiopathic short stature iss
The Journal of Clinical Endocrinology and Metabolism, 2011Co-Authors: Sara Benitosanz, Eva Barroso, Valeria Romanelli, Jordi Rosell, A. Aragones, María Caimari, Jesús Argente, Damian Heinesuner, Alfonso Hisadooliva, Judith L. RossAbstract:We report on the largest collection of SHOX duplications detected to date and discuss their potential association with Leri-Weill Dyschondrosteosis and idiopathic short stature.
-
Mesomelic and rhizomelic short stature: The phenotype of combined Leri-Weill Dyschondrosteosis and achondroplasia or hypochondroplasia.
American journal of medical genetics. Part A, 2003Co-Authors: Judith L. Ross, Charles I. Scott, Giedre Grigelioniene, Gary A. Bellus, Jack Abboudi, Andrew R. ZinnAbstract:We studied two children with combined genetic skeletal disorders. Both had Leri-Weill Dyschondrosteosis (LWD); one also had achondroplasia and the other had hypochondroplasia. Both had severe short stature and evidence of rhizomelia and mesomelia as well as other phenotypic features of their individual genetic disorders. Achondroplasia was due to the G380R FGF3R mutation and hypochondroplasia to a N540K mutation in the same gene. The patient with hypochondroplasia had a heterozygous SHOX deletion; no SHOX mutation was identified in the child with achondroplasia. The phenotypes of combined LWD and achondroplasia or hypochondroplasia appeared to be less than additive, suggesting that SHOX and FGFR3 act on overlapping pathways of bone growth and development.
-
Mesomelic and rhizomelic short stature: The phenotype of combined Leri-Weill Dyschondrosteosis and achondroplasia or hypochondroplasia.
American Journal of Medical Genetics Part A, 2002Co-Authors: Judith L. Ross, Charles I. Scott, Giedre Grigelioniene, Gary A. Bellus, Jack Abboudi, Andrew R. ZinnAbstract:We studied two children with combined genetic skeletal disorders. Both had Leri-Weill Dyschondrosteosis (LWD); one also had achondroplasia and the other had hypochondroplasia. Both had severe short stature and evidence of rhizomelia and mesomelia as well as other phenotypic features of their individual genetic disorders. Achondroplasia was due to the G380R FGF3R mutation and hypochondroplasia to a N540K mutation in the same gene. The patient with hypochondroplasia had a heterozygous SHOX deletion; no SHOX mutation was identified in the child with achondroplasia. The phenotypes of combined LWD and achondroplasia or hypochondroplasia appeared to be less than additive, suggesting that SHOX and FGFR3 act on overlapping pathways of bone growth and development. © 2002 Wiley-Liss, Inc.
-
Complete SHOX deficiency causes Langer mesomelic dysplasia.
American Journal of Medical Genetics, 2002Co-Authors: Andrew R. Zinn, Fanglin Wei, Ling Zhang, Frederick F.b. Elder, Charles I. Scott, Pia Marttila, Judith L. RossAbstract:The SHOX (short-stature homeobox-containing) gene encodes isoforms of a homeodomain transcription factor important in human limb development. SHOX haploinsufficiency has been implicated in three human growth disorders: Turner syndrome, idiopathic short stature, and Leri-Weill Dyschondrosteosis. Langer mesomelic dysplasia is thought to be the homozygous form of Dyschondrosteosis. However, complete SHOX deficiency has not been demonstrated for any postnatal patient with the classic Langer phenotype. We studied four adults and one child with Langer mesomelic dysplasia. SHOX abnormalities were detected in all five probands. One was a homozygote or hemizygote and two were compound heterozygotes. The homozygous or hemizygous mutation was in exon 6a, implying that the SHOXa isoform is essential for normal skeletal development. These findings confirm clinical inferences that Langer mesomelic dysplasia is the homozygous form of Leri-Weill Dyschondrosteosis and add to our understanding of genotype/phenotype relationships in SHOX deficiency disorders. © 2002 Wiley-Liss, Inc.
Céline Huber - One of the best experts on this subject based on the ideXlab platform.
-
Letters to the Editor SHOX point mutations in Dyschondrosteosis
2016Co-Authors: Céline Huber, V Cusin, M. Le Merrer, Michèle Mathieu, V Sulmont, Nathalie DagoneauAbstract:Dyschondrosteosis (DCS) has been recently ascribed to mutations of the SHOX gene on the pseudoautosomal region of the X and Y chro-mosomes.1 2 Most cases are accounted for by large scale deletions3–7 and only two point mutations have been hitherto identified in exon 4 (R195 X and Y199X1 2). Here, we show that point mutations in various regions of the SHOX gene also play an important role in the pathogenesis of the disease. A total of 22 aVected subjects belonging to eight families were included in the study. Inclusion criteria for aVected status were short stature (2 SD below normal) with short forelimbs and distal radioulnar deformity o
-
High incidence of SHOX anomalies in individuals with short stature
Journal of Medical Genetics, 2006Co-Authors: Céline Huber, Arnold Munnich, Myriam Rosilio, Valérie Cormier-daireAbstract:Objective: To study the SHOX gene and the PAR1 region in individuals with short stature. Methods: The study involved 56 cases of Dyschondrosteosis and 84 cases of idiopathic short stature (ISS). The study was designed to determine the following: the prevalence of SHOX anomalies in ISS; the frequency of Madelung deformity in individuals with SHOX anomalies; and the value of a family history of short stature in deciding whether to test for the SHOX gene. Results: 54 SHOX anomalies were observed, including 42 (68%) in the Dyschondrosteosis group and 12 (15%) in the ISS group. The high frequency of SHOX anomalies in the ISS group can be explained by the large proportion of boys in this group, reflecting the difficulty in diagnosing Dyschondrosteosis in young boys. Clinical evidence of Madelung deformity in six parents of ISS individuals emphasised the importance of family evaluation. Among the 54 SHOX anomalies, 33 PAR1 deletions were identified encompassing the SHOX gene (62%), one partial intragenic deletion (2%), nine deletions located downstream of the SHOX gene (16%), and 11 point mutations (20%). Conclusions: These data emphasise the value of using microsatellite markers located within and downstream of the SHOX gene.
-
Severe, atypical form of Dyschondrosteosis (report of two cases)
European Journal of Pediatrics, 2005Co-Authors: Tadeusz Bieganski, Valérie Cormier-daire, Céline Huber, Krzysztof Bik, Grzegorz Nowicki, Kazimierz KozlowskiAbstract:We report a mother and her son with unique mesomelic dysplasia. The mesomelic shortening in the upper extremities presents features of Leri-Weill syndrome (Dyschondrosteosis) (OMIM 127300), that of the lower extremities is consistent with Langer mesomelic dysplasia (OMIM 249700). Molecular studies showed a heterozygous short stature homeobox gene ( SHOX )deletion in both patients. A second genetic defect in the other SHOX allele was not found. Conclusion: Our study broadens the phenotypic spectrum associated with short stature homeobox gene functional haploinsufficiency.
-
allelic and nonallelic heterogeneity in Dyschondrosteosis leri weill syndrome
American Journal of Medical Genetics, 2001Co-Authors: Valerie Cormierdaire, Céline Huber, Arnold MunnichAbstract:Dyschondrosteosis (DCS) is an autosomal dominant form of mesomelic dysplasia that has been recently ascribed to large-scale deletions and nonsense mutations of the SHOX gene on the pseudoautosomal region of chromosome X and Y [Belin et al., 1998: Nat Genet 19:67–69; Shears et al., 1998: Nat Genet 19:70–73]. Here, we report the molecular analysis of a total of 23 DCS families including 16 previously reported pedigrees [Belin et al., 1998: Nat Genet 19:67–69; Huber et al., 2001: J Med Genet 38:281–284] and 7 novel DCS families. Linkage analyses in 21 of 23 families were consistent with linkage to the pseudoautosomal region. However, in 2 of 23 families, linkage studies excluded SHOX as the disease-causing gene, suggesting that this condition is genetically heterogeneous. © 2002 Wiley-Liss, Inc.
-
SHOX point mutations in Dyschondrosteosis
Journal of Medical Genetics, 2001Co-Authors: Céline Huber, V Cusin, M. Le Merrer, Arnold Munnich, Michèle Mathieu, V Sulmont, Nathalie Dagoneau, Valérie Cormier-daireAbstract:Dyschondrosteosis (DCS) has been recently ascribed to mutations of the SHOX gene on the pseudoautosomal region of the X and Y chromosomes.1 2 Most cases are accounted for by large scale deletions3-7 and only two point mutations have been hitherto identified in exon 4 (R195 X and Y199X1 2). Here, we show that point mutations in various regions of the SHOX gene also play an important role in the pathogenesis of the disease. A total of 22 affected subjects belonging to eight families were included in the study. Inclusion criteria for affected status were short stature (2 SD below normal) with short forelimbs …
H A Waldron - One of the best experts on this subject based on the ideXlab platform.
-
a case of Dyschondrosteosis from roman britain
Journal of Medical Genetics, 2000Co-Authors: H A WaldronAbstract:Editor—Dyschondrosteosis (Leri-Weill syndrome) is an autosomal dominant condition in which mesomelic short stature is associated with Madelung deformity of the radius.1-3 The expression of the condition is variable but consistently more severe in females and generally first appears in late childhood.4Patients with Dyschondrosteosis (DCS) have been found to have deletions and mutations of the short stature homeobox containing gene ( SHOX ).3 5-9 Homozygous mutations at the DCS locus results in the more severe Langer type of mesomelic dwarfism.10 I report here a case of DCS discovered in a skeleton from the Romano-British period, which may be the earliest case known at present. The skeleton was one of a small number of isolated burials excavated in 1998 from Crowland Road, Gloucester. The burials were in shallow graves, typically 0.4 m below the modern ground level and associated with structures dating to the 2nd or 3rd centuries AD. None of the burials was orientated west-east and therefore may be of pagan rather than Christian origin. Unfortunately the skeleton was damaged by earth moving equipment when the site was stripped and some further damage was sustained during excavation. Nevertheless, a photograph taken when the skeleton was still in situ clearly shows a Madelung deformity of the right forearm (fig 1). Figure 1 Photograph of skeleton of case of Dyschondrosteosis in the ground showing a Madelung deformity of the right radius. Note that the body appears to have been put into the grave without care. Damage to the left leg was caused by earth moving equipment and further damage was caused during excavation. Marker is 1 m and arrowhead points north. During recovery, some of the bones were damaged so that the amount of the skeleton which was available …
Arnold Munnich - One of the best experts on this subject based on the ideXlab platform.
-
High incidence of SHOX anomalies in individuals with short stature
Journal of Medical Genetics, 2006Co-Authors: Céline Huber, Arnold Munnich, Myriam Rosilio, Valérie Cormier-daireAbstract:Objective: To study the SHOX gene and the PAR1 region in individuals with short stature. Methods: The study involved 56 cases of Dyschondrosteosis and 84 cases of idiopathic short stature (ISS). The study was designed to determine the following: the prevalence of SHOX anomalies in ISS; the frequency of Madelung deformity in individuals with SHOX anomalies; and the value of a family history of short stature in deciding whether to test for the SHOX gene. Results: 54 SHOX anomalies were observed, including 42 (68%) in the Dyschondrosteosis group and 12 (15%) in the ISS group. The high frequency of SHOX anomalies in the ISS group can be explained by the large proportion of boys in this group, reflecting the difficulty in diagnosing Dyschondrosteosis in young boys. Clinical evidence of Madelung deformity in six parents of ISS individuals emphasised the importance of family evaluation. Among the 54 SHOX anomalies, 33 PAR1 deletions were identified encompassing the SHOX gene (62%), one partial intragenic deletion (2%), nine deletions located downstream of the SHOX gene (16%), and 11 point mutations (20%). Conclusions: These data emphasise the value of using microsatellite markers located within and downstream of the SHOX gene.
-
allelic and nonallelic heterogeneity in Dyschondrosteosis leri weill syndrome
American Journal of Medical Genetics, 2001Co-Authors: Valerie Cormierdaire, Céline Huber, Arnold MunnichAbstract:Dyschondrosteosis (DCS) is an autosomal dominant form of mesomelic dysplasia that has been recently ascribed to large-scale deletions and nonsense mutations of the SHOX gene on the pseudoautosomal region of chromosome X and Y [Belin et al., 1998: Nat Genet 19:67–69; Shears et al., 1998: Nat Genet 19:70–73]. Here, we report the molecular analysis of a total of 23 DCS families including 16 previously reported pedigrees [Belin et al., 1998: Nat Genet 19:67–69; Huber et al., 2001: J Med Genet 38:281–284] and 7 novel DCS families. Linkage analyses in 21 of 23 families were consistent with linkage to the pseudoautosomal region. However, in 2 of 23 families, linkage studies excluded SHOX as the disease-causing gene, suggesting that this condition is genetically heterogeneous. © 2002 Wiley-Liss, Inc.
-
SHOX point mutations in Dyschondrosteosis
Journal of Medical Genetics, 2001Co-Authors: Céline Huber, V Cusin, M. Le Merrer, Arnold Munnich, Michèle Mathieu, V Sulmont, Nathalie Dagoneau, Valérie Cormier-daireAbstract:Dyschondrosteosis (DCS) has been recently ascribed to mutations of the SHOX gene on the pseudoautosomal region of the X and Y chromosomes.1 2 Most cases are accounted for by large scale deletions3-7 and only two point mutations have been hitherto identified in exon 4 (R195 X and Y199X1 2). Here, we show that point mutations in various regions of the SHOX gene also play an important role in the pathogenesis of the disease. A total of 22 affected subjects belonging to eight families were included in the study. Inclusion criteria for affected status were short stature (2 SD below normal) with short forelimbs …
-
Allelic and nonallelic heterogeneity in Dyschondrosteosis (Leri‐Weill syndrome)
American Journal of Medical Genetics, 2001Co-Authors: Valérie Cormier-daire, Céline Huber, Arnold MunnichAbstract:Dyschondrosteosis (DCS) is an autosomal dominant form of mesomelic dysplasia that has been recently ascribed to large-scale deletions and nonsense mutations of the SHOX gene on the pseudoautosomal region of chromosome X and Y [Belin et al., 1998: Nat Genet 19:67–69; Shears et al., 1998: Nat Genet 19:70–73]. Here, we report the molecular analysis of a total of 23 DCS families including 16 previously reported pedigrees [Belin et al., 1998: Nat Genet 19:67–69; Huber et al., 2001: J Med Genet 38:281–284] and 7 novel DCS families. Linkage analyses in 21 of 23 families were consistent with linkage to the pseudoautosomal region. However, in 2 of 23 families, linkage studies excluded SHOX as the disease-causing gene, suggesting that this condition is genetically heterogeneous. © 2002 Wiley-Liss, Inc.
-
SHOX gene mutations and deletions in Dyschondrosteosis or Leri-Weill syndrome.
Acta paediatrica (Oslo Norway : 1992). Supplement, 1999Co-Authors: Valérie Cormier-daire, V Belin, V Cusin, Géraldine Viot, D Girlich, Annick Toutain, Anne Moncla, Michel Vekemans, M. Le Merrer, Arnold MunnichAbstract:Dyschondrosteosis is an autosomal dominant form of mesomelic dysplasia that is often combined with a deformity of the forearms called Madelung deformity. Based on the observation of X-Y translocations (p22,q12) in patients with Dyschondrosteosis, the authors tested the pseudoautosomal region in eight affected families and showed linkage of the Dyschondrosteosis gene to a microsatellite DNA marker at the DXYS233 locus (Zmax = 6.26 at theta = 0). Since the short stature homeobox-containing gene (SHOX) involved in idiopathic growth retardation and possibly Turner syndrome maps to this region, SHOX was regarded as a strong candidate gene for Dyschondrosteosis. This article reports the detection of large-scale SHOX deletions in seven of the eight families and a nonsense mutation of SHOX in the remaining family affected with Dyschondrosteosis. Additional evidence suggests that Langer mesomelic dwarfism results from homozygous mutations at the genetic locus responsible for Dyschondrosteosis.
Valérie Cormier-daire - One of the best experts on this subject based on the ideXlab platform.
-
High incidence of SHOX anomalies in individuals with short stature
Journal of Medical Genetics, 2006Co-Authors: Céline Huber, Arnold Munnich, Myriam Rosilio, Valérie Cormier-daireAbstract:Objective: To study the SHOX gene and the PAR1 region in individuals with short stature. Methods: The study involved 56 cases of Dyschondrosteosis and 84 cases of idiopathic short stature (ISS). The study was designed to determine the following: the prevalence of SHOX anomalies in ISS; the frequency of Madelung deformity in individuals with SHOX anomalies; and the value of a family history of short stature in deciding whether to test for the SHOX gene. Results: 54 SHOX anomalies were observed, including 42 (68%) in the Dyschondrosteosis group and 12 (15%) in the ISS group. The high frequency of SHOX anomalies in the ISS group can be explained by the large proportion of boys in this group, reflecting the difficulty in diagnosing Dyschondrosteosis in young boys. Clinical evidence of Madelung deformity in six parents of ISS individuals emphasised the importance of family evaluation. Among the 54 SHOX anomalies, 33 PAR1 deletions were identified encompassing the SHOX gene (62%), one partial intragenic deletion (2%), nine deletions located downstream of the SHOX gene (16%), and 11 point mutations (20%). Conclusions: These data emphasise the value of using microsatellite markers located within and downstream of the SHOX gene.
-
Severe, atypical form of Dyschondrosteosis (report of two cases)
European Journal of Pediatrics, 2005Co-Authors: Tadeusz Bieganski, Valérie Cormier-daire, Céline Huber, Krzysztof Bik, Grzegorz Nowicki, Kazimierz KozlowskiAbstract:We report a mother and her son with unique mesomelic dysplasia. The mesomelic shortening in the upper extremities presents features of Leri-Weill syndrome (Dyschondrosteosis) (OMIM 127300), that of the lower extremities is consistent with Langer mesomelic dysplasia (OMIM 249700). Molecular studies showed a heterozygous short stature homeobox gene ( SHOX )deletion in both patients. A second genetic defect in the other SHOX allele was not found. Conclusion: Our study broadens the phenotypic spectrum associated with short stature homeobox gene functional haploinsufficiency.
-
SHOX point mutations in Dyschondrosteosis
Journal of Medical Genetics, 2001Co-Authors: Céline Huber, V Cusin, M. Le Merrer, Arnold Munnich, Michèle Mathieu, V Sulmont, Nathalie Dagoneau, Valérie Cormier-daireAbstract:Dyschondrosteosis (DCS) has been recently ascribed to mutations of the SHOX gene on the pseudoautosomal region of the X and Y chromosomes.1 2 Most cases are accounted for by large scale deletions3-7 and only two point mutations have been hitherto identified in exon 4 (R195 X and Y199X1 2). Here, we show that point mutations in various regions of the SHOX gene also play an important role in the pathogenesis of the disease. A total of 22 affected subjects belonging to eight families were included in the study. Inclusion criteria for affected status were short stature (2 SD below normal) with short forelimbs …
-
Allelic and nonallelic heterogeneity in Dyschondrosteosis (Leri‐Weill syndrome)
American Journal of Medical Genetics, 2001Co-Authors: Valérie Cormier-daire, Céline Huber, Arnold MunnichAbstract:Dyschondrosteosis (DCS) is an autosomal dominant form of mesomelic dysplasia that has been recently ascribed to large-scale deletions and nonsense mutations of the SHOX gene on the pseudoautosomal region of chromosome X and Y [Belin et al., 1998: Nat Genet 19:67–69; Shears et al., 1998: Nat Genet 19:70–73]. Here, we report the molecular analysis of a total of 23 DCS families including 16 previously reported pedigrees [Belin et al., 1998: Nat Genet 19:67–69; Huber et al., 2001: J Med Genet 38:281–284] and 7 novel DCS families. Linkage analyses in 21 of 23 families were consistent with linkage to the pseudoautosomal region. However, in 2 of 23 families, linkage studies excluded SHOX as the disease-causing gene, suggesting that this condition is genetically heterogeneous. © 2002 Wiley-Liss, Inc.
-
SHOX gene mutations and deletions in Dyschondrosteosis or Leri-Weill syndrome.
Acta paediatrica (Oslo Norway : 1992). Supplement, 1999Co-Authors: Valérie Cormier-daire, V Belin, V Cusin, Géraldine Viot, D Girlich, Annick Toutain, Anne Moncla, Michel Vekemans, M. Le Merrer, Arnold MunnichAbstract:Dyschondrosteosis is an autosomal dominant form of mesomelic dysplasia that is often combined with a deformity of the forearms called Madelung deformity. Based on the observation of X-Y translocations (p22,q12) in patients with Dyschondrosteosis, the authors tested the pseudoautosomal region in eight affected families and showed linkage of the Dyschondrosteosis gene to a microsatellite DNA marker at the DXYS233 locus (Zmax = 6.26 at theta = 0). Since the short stature homeobox-containing gene (SHOX) involved in idiopathic growth retardation and possibly Turner syndrome maps to this region, SHOX was regarded as a strong candidate gene for Dyschondrosteosis. This article reports the detection of large-scale SHOX deletions in seven of the eight families and a nonsense mutation of SHOX in the remaining family affected with Dyschondrosteosis. Additional evidence suggests that Langer mesomelic dwarfism results from homozygous mutations at the genetic locus responsible for Dyschondrosteosis.