Cryptic intragenic deletion of the SHOX gene in a family with Léri-Weill dyschondrosteosis detected by Multiplex Ligation-Dependent Probe Amplification (MLPA)

Funari, Mariana F A; Jorge, Alexander A. L.; Pinto, Emília M.; Arnhold, Ivo Jorge Prado; Mendonça, Berenice Bilharinho; Nishi, Mirian Yumie

doi:10.1590/s0004-27302008000800029

Cited by 13 publications

(7 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Further reports include pedigrees indicating a recombination event in PAR1 (e.g. the transmission of a SHOX deficiency from father to son and daughter), but the authors neither discuss the recombination events in PAR1 and the resulting ‘pseudoautosomal inheritance’ nor differentiate between a Y‐ and X‐chromosomal SHOX mutation (21–24).…”

Section: Discussionmentioning

confidence: 99%

Pseudoautosomal inheritance of Léri-Weill syndrome: what does it mean?

et al. 2011

View full text Add to dashboard Cite

The short stature homeobox (SHOX) gene is located in the pseudoautosomal region 1 of both sex chromosomes. Haploinsufficiency of SHOX leads to different phenotypes ranging from isolated short stature to Léri-Weill syndrome characterized by short stature, mesomelia and Madelung deformity. We describe a family with a SHOX deletion originally located on the Y chromosome and transmitted from father to daughter by crossover during meiosis. The male index patient presented with short stature, mesomelia and mild Madelung deformity. His father had a normal height but slightly disproportionate short legs. The sister of the index patient presented with marked Madelung deformity and normal height. A deletion of the SHOX gene was identified in the male index patient, his father and his sister. Metaphase fluorescence in situ hybridization (FISH) analyses showed a deletion of the SHOX gene on the Y chromosomes of the index patient and his father, and on the X chromosome of his sister, indicating that a meiotic crossover of the SHOX gene region between the X and Y chromosomes had occurred. The pseudoautosomal region 1 is a known recombination 'hot spot' in male meiosis. Published genetic maps indicate high recombination frequency of ∼40% for SHOX in male meiosis leading to pseudoautosomal inheritance.

show abstract

Section: Discussionmentioning

confidence: 99%

Pseudoautosomal inheritance of Léri-Weill syndrome: what does it mean?

et al. 2011

View full text Add to dashboard Cite

show abstract

“…IGV visualization also enabled the identification of deletion breakpoints in some cases ( Figure 2): Case 11 had a previously reported intragenic deletion involving exons 4, 5, and 6a; however, its breakpoints had not been defined. 9 After the IGV visualization, we designed specific primers and sequenced the region across the deletion breakpoints. The deletion was defined in 11 722 bp, with 4 bp overlapping in both breakpoints.…”

Section: Validationmentioning

confidence: 99%

Evaluation of SHOX defects in the era of next‐generation sequencing

et al. 2019

Self Cite

View full text Add to dashboard Cite

Short stature homeobox (SHOX) haploinsufficiency is a frequent cause of short stature. Despite advances in sequencing technologies, the identification of SHOX mutations continues to be performed using standard methods, including multiplex ligation‐dependent probe amplification (MLPA) followed by Sanger sequencing. We designed a targeted panel of genes associated with growth impairment, including SHOX genomic and enhancer regions, to improve the resolution of next‐generation sequencing for SHOX analysis. We used two software packages, CONTRA and Nexus Copy Number, in addition to visual analysis to investigate the presence of copy number variants (CNVs). We evaluated 15 patients with previously known SHOX defects, including point mutations, deletions and a duplication, and 77 patients with idiopathic short stature (ISS). The panel was able to confirm all known defects in the validation analysis. During the prospective evaluation, we identified two new partial SHOX deletions (one detected only by visual analysis), including an intragenic deletion not detected by MLPA. Additionally, we were able to determine the breakpoints in four cases. Our results show that the designed panel can be used for the molecular investigation of patients with ISS, and it may even detect CNVs in SHOX and its enhancers, which may be present in a significant fraction of patients.

show abstract

“…GCK deletions in MODY2) and in short stature (e.g. SHOX deletion) 22 . More recently, the advent of microarray technologies has allowed the investigation of CNVs in genomic scale using techniques such as array Comparative Genomic Hybridization (aCGH) or Single Nucleotide Polymorphism (SNP) arrays.…”

Section: Searching For Chromosomal Abnormalities Large Indels and Comentioning

confidence: 99%

Diagnóstico molecular na prática clínica: visão do endocrinologista

Ferraz-de-Souza¹

2015

Rev. Med. (São Paulo)

View full text Add to dashboard Cite

Endocrinology is one of several medical specialities that have been gradually transformed by a deeper understanding of the molecular bases of disorders. Genetic testing with the purposes of defining a precise molecular diagnosis has increasingly gained space in the routine assessment of patients with endocrinopathies, and the advent of massive parallel sequencing (MPS) is boosting the incorporation of molecular information in the clinic. The main benefit of genetic testing is diagnostic precision, resulting in improved and individualized care for patients and family members, and better disease prevention. However, genetic tests are not infallible and may bear several potential risks, being thus indicated when clinical suspicion is strong and the benefit of determining a molecular diagnosis is unambiguous. In this review, these evolving concepts and current indications for molecular diagnosis in endocrinology will be explored. Molecular tools will be revised and contextualised, including those aimed at identifying changes in gene dosage (karyotpe, FISH, MLPA, aCGH, SNParray) or in the DNA nucleotide sequence (allele-specific PCR, RFLP, Sanger sequencing, MPS or NGS). Finally, matters surrounding the complex attribution of biologically relevant functional impact to identified DNA variants will be explored, together with the challenges brought by high throughput molecular analysis. These are exciting times for molecular endocrinology, and hopefully soon a translation to multiple benefits for patients will be self-evident.Keywords: Genetic testing; Endocrinology; Mutation; DNA mutation analysis; Transcription, genetic; Genetic markers; Sequence analysis, DNA/methdos; Molecular sequence data. RESUMO:A endocrinologia é uma de muitas especialidades médicas que vem sendo transformada pelo maior conhecimento das bases moleculares das doenças. O teste genético com o propósito de definir o diagnóstico molecular vem ganhando espaço na avaliação rotineira de pacientes com endocrinopatias, e o advento do sequenciamento paralelelo em larga escala (SPLE) está ampliando o potencial de incorporação da informação molecular na prática clínica. O principal benefício do teste genético é a precisão diagnóstica, resultando em melhora e individualização do tratamento de pacientes e seus familiares, e da prevenção de doenças. Entretanto, testes genéticos não são infalíveis e podem trazer alguns riscos potenciais, estando portanto indicados quando a suspeita clínica é forte e o benefício do diagnóstico molecular é claro. Nesta revisão serão explorados conceitos genéticos em evolução e as atuais indicações de diagnóstico molecular em endocrinologia. Ferramentas moleculares serão revisadas, incluindo aquelas visando a identificação de alterações no número de cópias gênicas (cariótipo, FISH, MLPA, aCGH, SNParray) ou na sequencia nucleotídica do DNA (PCR alelo-específica, RFLP, sequenciamento Sanger, SPLE ou NGS). Ainda, serão discutidos os percalços da difícil atribuição de impacto funcional e relevância biológica a variantes de DN...

show abstract

Cryptic intragenic deletion of the SHOX gene in a family with Léri-Weill dyschondrosteosis detected by Multiplex Ligation-Dependent Probe Amplification (MLPA)

Cited by 13 publications

References 15 publications

Pseudoautosomal inheritance of Léri-Weill syndrome: what does it mean?

Pseudoautosomal inheritance of Léri-Weill syndrome: what does it mean?

Evaluation of SHOX defects in the era of next‐generation sequencing

Diagnóstico molecular na prática clínica: visão do endocrinologista

Contact Info

Product

Resources

About