Mutational screening of EXT1 and EXT2 genes in Polish patients with hereditary multiple exostoses

Jamsheer, Aleksander; Socha, Magdalena; Sowińska‐Seidler, Anna; Telega, Kinga; Trzeciak, Tomasz; Latos‐Bieleńska, Anna

doi:10.1007/s13353-014-0195-z

Cited by 32 publications

(26 citation statements)

References 27 publications

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“…In a first analysis of HME patients in Poland, Jamsheer et al investigated 33 unrelated HME patients (62). Using Sanger sequencing and MLPA, they detected a heterozygous mutation in the coding exons of EXT1 or EXT2 in about 55% and 30% of patients, respectively, with 15 mutations being novel.…”

Section: Spectrum and Roles Of Ext Mutationsmentioning

confidence: 99%

Hereditary Multiple Exostoses: New Insights into Pathogenesis, Clinical Complications, and Potential Treatments

Pacifici

2017

Curr Osteoporos Rep

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Purpose of review Hereditary Multiple Exostoses (HME) is a complex musculoskeletal pediatric disorder characterized by osteochondromas that form next to the growth plates of many skeletal elements, including long bones, ribs and vertebrae. Due to its intricacies and unresolved issues, HME continues to pose major challenges to both clinicians and biomedical researchers. The purpose of this review is to describe and analyze recent advances in this field and point to possible targets and strategies for future biologically-based therapeutic intervention. Recent findings Most HME cases are linked to loss-of-function mutations in EXT1 or EXT2 that encode glycosyltrasferases responsible for heparan sulfate (HS) synthesis, leading to HS deficiency. Recent genomic inquires have extended those findings, but have yet to provide a definitive genotype-phenotype correlation. Clinical studies emphasize that in addition to the well-known skeletal problems caused by the osteochondromas; HME patients can experience, and suffer from, other symptoms and health complications such as chronic pain and nerve impingement. Laboratory work has produced novel insights into alterations in cellular and molecular mechanisms instigated by HS deficiency and subtending onset and growth of osteochondroma and how such changes could be targeted toward therapeutic ends. Summary HME is a rare and orphan disease and as such, is being studied only by a handful of clinical and basic investigators. Despite this limitation, significant advances have been made in the last few years, and the future bodes well for deciphering more thoroughly its pathogenesis and in turn, identifying a most effective treatment for osteochondroma prevention.

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Section: Spectrum and Roles Of Ext Mutationsmentioning

confidence: 99%

Hereditary Multiple Exostoses: New Insights into Pathogenesis, Clinical Complications, and Potential Treatments

Pacifici

2017

Curr Osteoporos Rep

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“…In our study, mutations in EXT1 gene were found in 55% of probands. It is a much less than 85% found in 33 unrelated Polish patients (Jamsheer et al, 2014). Mutations in EXT2 gene were found in two probands.…”

Section: D Ementioning

confidence: 87%

Hereditary Multiple Exostoses: Clinical, Molecular and Radiologic Survey in 9 Families

et al. 2017

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Abstract:Hereditary multiple exostoses (HME) represents a heterogeneous group of diseases often associated with progressive skeletal deformities. Most frequently, mutations in EXT1 and EXT2 genes with autosomal dominant inheritance are responsible for HME. In our group of 9 families with HME we evaluated the clinical course of the disease and analysed molecular background using Sanger sequencing and MLPA in EXT1 and EXT2 genes. The mean age in our group of patients, when the first exostosis was recognised was 4.5 years (range 2-10 years) and the number of exostoses per one patient documented on X-ray ranged from 2 to 54. Most of the exostoses developed before the growth was completed and they were dominantly localised in the distal femurs, proximal tibia, proximal humerus and distal radius. In all patients, at least one to 8 surgeries were necessary due to complaints and local complications, but neither patient

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“…5 Son causadas principalmente por mutaciones en genes supresores de tumores, como el EXT1, localizado en 8q24.11, que causa la EMH tipo 1 (OMIM 133700); el EXT2, ubicado en 11p11.2, que causa la EMH tipo 2 (OMIM 133701); y la EMH tipo 3 (OMIM 600209), cuyo locus ha sido localizado en el brazo corto del cromosoma 19 (19p), pero aún no se han detectado alteraciones de este. 1,6,7 Las mutaciones en EXT1 representan entre 56 y 78% Se presenta el caso de una adolescente evaluada de forma multidisciplinaria con diagnóstico clínico, estudio radiológico y molecular de EMH con doble alelo mutante en el gen EXT1 no informado previamente.…”

Section: A S F O R M a S H E R E D I T A R I A S D E E X O S T O S unclassified

Alelo doble mutante en el gen EXT1 no informado previamente en una adolescente con exostosis múltiple hereditaria

et al. 2015

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Presentación de casos clínicos RESUMENLas formas hereditarias de exostosis múltiple, actualmente denominada EXT1/EXT2-CDG dentro de los desórdenes congénitos de la glicosilación, son los tumores óseos benignos más comunes y se caracterizan por la formación de lesiones óseas cubiertas de cartílago, localizadas en yuxtaposición a epífisis de huesos largos, aunque, en los casos graves, pueden presentar una amplia distribución. El inicio es variable desde los 2-3 años hasta los 13-15 y presenta una incidencia estimada que va de 1/18 000 a 1/50 000 casos en los países europeos. Se presenta el caso de un doble alelo mutante en el gen EXT1 no informado previamente en una adolescente y su familia con exostosis múltiple hereditaria. Palabras clave: exostosis múltiple hereditaria, EXT1/EXT2-CDG. ABSTRACTHereditary forms of multiple exostoses, now called EXT1/ EXT2-CDG within Congenital Disorders of Glycosylation, are the most common benign bone tumors in humans and clinical description consists of the formation of several cartilagecapped bone tumors, usually benign and localized in the juxta-epiphyseal region of long bones, although wide body dissemination in severe cases is not uncommon. Onset of the Alelo doble mutante en el gen EXT1 no informado previamente en una adolescente con exostosis múltiple hereditaria Double mutant alleles in the EXT1 gene not previously reported in a teenager with hereditary multiple exostoses disease is variable ranging from 2-3 years up to 13-15 years with an estimated incidence ranging from 1/18 000 to 1/50 000 cases in European countries. We present a double mutant alleles in the EXT1 gene not previously reported in a teenager and her family with hereditary multiple exostoses.

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Mutational screening of EXT1 and EXT2 genes in Polish patients with hereditary multiple exostoses

Cited by 32 publications

References 27 publications

Hereditary Multiple Exostoses: New Insights into Pathogenesis, Clinical Complications, and Potential Treatments

Hereditary Multiple Exostoses: New Insights into Pathogenesis, Clinical Complications, and Potential Treatments

Hereditary Multiple Exostoses: Clinical, Molecular and Radiologic Survey in 9 Families

Alelo doble mutante en el gen EXT1 no informado previamente en una adolescente con exostosis múltiple hereditaria

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