scholarly journals Cytogenetic and Molecular Genetic Characterization of Children with Short Stature / Citogenetska in Molekularno Genetska Opredelitev Nizke Rasti Pri Otrocih

2015 ◽  
Vol 54 (2) ◽  
pp. 98-102 ◽  
Author(s):  
Tinka Hovnik ◽  
Darja Šmigoc Schweiger ◽  
Primož Kotnik ◽  
Jernej Kovač ◽  
Tadej Battelino ◽  
...  
Keyword(s):  
Short Stature ◽  
Gene Deletion ◽  
Mutation Screening ◽  
Molecular Genetic ◽  
Point Mutations ◽  
Idiopathic Short Stature ◽  
Fish Analysis ◽  
Coding Region ◽  
Exon 2 ◽  
Shox Gene

Abstract Background. The deficiency of SHOX gene (short stature homeobox-containing gene) has been recognized as the most frequent monogenetic cause of short stature. SHOX gene has been associated with short stature in Turner syndrome and Leri Weill dyschondrosteosis as well with non-syndromic idiopathic short stature. The aim of this study was to determine the frequency of SHOX deletions and mutations in a cohort of Slovenian children with short stature, and to delineate indications for routine SHOX gene mutation screening. Methods and results. 40 selected subjects with idiopathic short stature were screened for entire SHOX gene deletion and for mutations in the SHOX gene coding region (exon 2 to 6), together with sequences flanking the exon-intron boundaries. FISH analysis on metaphase and interphase spreads revealed no entire gene deletion. Additionally, no pathogenic point mutations or smaller deletion/duplications were identified in this study group. Conclusions. SHOX gene deletions and point mutations are not a common cause of idiopathic short stature in a cohort of Slovenian children with short stature. Therefore, the frequency of SHOX mutations must be much lower as expected based on the reported data.

scholarly journals Improved Molecular Diagnostics of Idiopathic Short Stature and Allied Disorders: Quantitative Polymerase Chain Reaction-Based Copy Number Profiling of SHOX and Pseudoautosomal Region 1

2010 ◽  
Vol 95 (6) ◽  
pp. 3010-3018 ◽  
Author(s):  
Barbara D'haene ◽  
Jan Hellemans ◽  
Margarita Craen ◽  
Jean De Schepper ◽  
Koen Devriendt ◽  
...  
Keyword(s):  
Short Stature ◽  
Molecular Diagnostics ◽  
Copy Number ◽  
Quantitative Polymerase Chain Reaction ◽  
Molecular Genetic ◽  
Significant Proportion ◽  
Idiopathic Short Stature ◽  
Pseudoautosomal Region ◽  
Shox Gene ◽  
Copy Number Changes

Abstract Context: Short stature has an incidence of three in 100 in children. Reliable molecular genetic testing may be crucial in the context of beneficial disease management. Deletions spanning or surrounding the SHOX gene account for a significant proportion of patients with idiopathic short stature (ISS) and allied disorders, such as Leri-Weill dyschondrosteosis. Objective: Several shortcomings of current strategies for copy number profiling of the SHOX region prompted us to develop an improved test for molecular diagnostics of the SHOX region. Design and Results: We introduced a quantitative PCR (qPCR)-based copy number profiling test, consisting of 11 amplicons targeting clinically relevant regions, i.e. the SHOX gene and regulatory regions. To ensure an optimal sensitivity and specificity, this test was validated in 32 controls and 18 probands with previously identified copy number changes. In addition, 152 probands with SHOX-associated phenotypes were screened, revealing 10 novel copy number changes. Conclusion: This highly validated qPCR test supersedes other approaches for copy number screening of the SHOX region in terms of reliability, accuracy, and cost efficiency. In addition, another strong point is the fact that it can be easily implemented in any standard equipped molecular laboratory. Our qPCR-based test is highly recommended for molecular diagnostics of idiopathic short stature and allied disorders.

scholarly journals Next generation sequencing-based mutation screening of 86 patients with idiopathic short stature

2017 ◽  
Vol 64 (10) ◽  
pp. 947-954 ◽  
Author(s):  
Atsushi Hattori ◽  
Yuko Katoh-Fukui ◽  
Akie Nakamura ◽  
Keiko Matsubara ◽  
Tsutomu Kamimaki ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Short Stature ◽  
Mutation Screening ◽  
Idiopathic Short Stature ◽  
Next Generation ◽  
Generation Sequencing

scholarly journals Screening of SHOX gene sequence variants in Saudi Arabian children with idiopathic short stature

2017 ◽  
Vol 60 (10) ◽  
pp. 327 ◽  
Author(s):  
Abdulla A. Alharthi ◽  
Ehab I. El-Hallous ◽  
Iman M. Talaat ◽  
Hamed A. Alghamdi ◽  
Matar I. Almalki ◽  
...  
Keyword(s):  
Short Stature ◽  
Gene Sequence ◽  
Saudi Arabian ◽  
Idiopathic Short Stature ◽  
Sequence Variants ◽  
Shox Gene

scholarly journals Auxology Is a Valuable Instrument for the Clinical Diagnosis of SHOX Haploinsufficiency in School-Age Children with Unexplained Short Stature

2003 ◽  
Vol 88 (10) ◽  
pp. 4891-4896 ◽  
Author(s):  
Gerhard Binder ◽  
Michael B. Ranke ◽  
David D. Martin
Keyword(s):  
Short Stature ◽  
De Novo ◽  
Fragment Size ◽  
Mutation Screening ◽  
Idiopathic Short Stature ◽  
Paternal Allele ◽  
Leg Length ◽  
Sitting Height ◽  
Arm Span ◽  
Hand Radiography

Abstract SHOX (short stature homeobox-containing gene) mutations causing haploinsufficiency have been reported in some individuals with idiopathic short stature and in many patients with Leri-Weill-dyschondrosteosis. Around 80% of SHOX mutations are complete gene deletions, whereas diverse point mutations account for the rest. The aim of this study was to estimate the prevalence of SHOX mutations in children with idiopathic short stature and to give an unbiased characterization of the haploinsufficiency phenotype of such children. We recruited 140 children (61 girls), in our clinic, with idiopathic short stature, which was defined by the presence of normal IGF-I and free T4; a normal karyotype in females; the absence of endomysium antibodies, of chronic organic, psychological, or syndromatic disease; and by the lack of clear signs of any osteodysplasia. Height, arm span, and sitting height were recorded, and subischial leg length was calculated. Two highly polymorphic microsatellite markers located around the SHOX coding region (CA-SHOX repeat and DXYS233) were PCR-amplified with fluorescent primers and separated in an automatic sequencing machine. Analysis of parental DNA was performed in the probands who had only one fragment size of each of both markers. SHOX haploinsufficiency caused by a SHOX deletion was confirmed in three probands (2%), all females, who carried a de novo deletion through loss of the paternal allele. Their auxological data revealed a significant shortening of arms and legs in the presence of a low-normal sitting height, when compared with the other 137 children tested. Therefore, the extremities-trunk ratio (sum of leg length and arm span, divided by sitting height) for total height was significantly lower in the three SHOX haploinsufficient probands, in comparison with the whole group. This observation was confirmed with the auxological data of five additional patients (four females) previously diagnosed with SHOX haploinsufficiency; all but the youngest girl had height-adjusted extremities-trunk ratios more than 1 sd below the mean. All children with SHOX haploinsufficiency exhibited at least one characteristic radiological sign of Leri-Weill-dyschondrosteosis in their left-hand radiography, namely triangularization of the distal radial epiphysis, pyramidalization of the distal carpal row, or lucency of the distal ulnar border of the radius. Our observations suggest that it is rational to limit SHOX mutation screening to children with an extremities-trunk ratio less than 1.95 + 1/2 height (m) and to add a critical judgment of the hand radiography.

scholarly journals Investigation of SHOX Gene Mutations in Turkish Patients with Idiopathic Short Stature

2016 ◽  
Vol 8 (2) ◽  
pp. 144-149 ◽  
Author(s):  
Kenan Delil ◽  
Halil Gürhan Karabulut ◽  
Bülent Hacıhamdioğlu ◽  
Zeynep Şıklar ◽  
Merih Berberoğlu ◽  
...  
Keyword(s):  
Short Stature ◽  
Gene Mutations ◽  
Idiopathic Short Stature ◽  
Shox Gene ◽  
Turkish Patients

scholarly journals SHOX gene and conserved noncoding element deletions/duplications in C olombian patients with idiopathic short stature

2013 ◽  
Vol 2 (2) ◽  
pp. 95-102 ◽  
Author(s):  
Gloria Tatiana Vinasco Sandoval ◽  
Giovanna Carola Jaimes ◽  
Mauricio Coll Barrios ◽  
Camila Cespedes ◽  
Harvy Mauricio Velasco
Keyword(s):  
Short Stature ◽  
Idiopathic Short Stature ◽  
Shox Gene

Detection of SHOX gene deletions in Egyptian children with idiopathic short stature using FISH

Meta Gene ◽  
2020 ◽  
Vol 24 ◽  
pp. 100697
Author(s):  
Amr Shujaa-Addin ◽  
Mervat Hashish ◽  
Nahla Nazmy ◽  
Amany Srour ◽  
Ebtesam Abdalla
Keyword(s):  
Short Stature ◽  
Idiopathic Short Stature ◽  
Gene Deletions ◽  
Shox Gene ◽  
Egyptian Children

scholarly journals Heterozygous Deletion in Exons 4-5 of SHOX Gene in a Patient Diagnosed as Idiopathic Short Stature

2017 ◽  
Vol 63 (3) ◽  
pp. 155-158 ◽  
Author(s):  
Anna David ◽  
Imre Zoltán Kun ◽  
Gábor Nyírő ◽  
Zsuzsánna Szántó ◽  
Attila Patócs
Keyword(s):  
Short Stature ◽  
Tanner Stage ◽  
Thyroid Stimulating Hormone ◽  
Idiopathic Short Stature ◽  
Breast Development ◽  
Heterozygous Deletion ◽  
Shox Gene ◽  
Sitting Height ◽  
History Of ◽  
Stage 1

AbstractIntroduction: Isolated Short Stature Homeobox (SHOX) gene haploinsufficiency can be found in 2-15% of individuals diagnosed with idiopathic short stature determining different skeletal phenotypes.Case presentation: We present the history of an 11-year-old female patient diagnosed with idiopathic short stature. Clinically, she was moderately disproportionate, with cubitus valgus and palatum ogivale. Her breast development was in Tanner stage 1 at the time of diagnosis. The endocrine diagnostic tests did not reveal any abnormalities except a slightly elevated thyroid stimulating hormone. We have also assessed the bone radiological findings. Multiplex Ligation-dependent Probe Amplification technique used for the identification of SHOX gene haploinsufficiency showed a heterozygous deletion spanning exons 4-5 of SHOX gene.Conclusions: This case is determined by deletions in exons 4-5 of SHOX gene and indicates the necessity of screening for SHOX deletions in patients diagnosed with idiopathic short stature, especially in children having increased sitting height-to-height ratio or decreased extremities-to-trunk ratio.

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