Identification of a novel 15.5 kb SHOX deletion associated with marked intrafamilial phenotypic variability and analysis of its molecular origin
| Autor: | M. Tryfonidis, Carolina Sismani, Ioanna Alexandrou, Eleni Zamba-Papanicolaou, Nicos Skordis, Angelos Alexandrou, Violetta Christophidou-Anastasiadou, George Koumbaris, Vassos Neocleous, Kyriakos Tsangaras, Ioannis Papaevripidou, Leonidas A. Phylactou, George A. Tanteles |
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| Rok vydání: | 2016 |
| Předmět: |
Adult
Male 0301 basic medicine Alu element Biology Osteochondrodysplasias Short stature Translocation Genetic Chromosome Breakpoints Young Adult 03 medical and health sciences Exon Short Stature Homeobox Protein Alu Elements Genes X-Linked Genetics medicine Humans Coding region Multiplex ligation-dependent probe amplification 10. No inequality Genetic Association Studies Growth Disorders Sequence Deletion Homeodomain Proteins Comparative Genomic Hybridization Base Sequence Point mutation Sequence Analysis DNA Chromosome Banding Pedigree Phenotype 030104 developmental biology Female medicine.symptom Haploinsufficiency |
| Zdroj: | Journal of Genetics |
| ISSN: | 0022-1333 |
| DOI: | 10.1007/s12041-016-0698-y |
| Popis: | Haploinsufficiency of the short stature homeobox contaning SHOX gene has been shown to result in a spectrum of phenotypes ranging from Leri-Weill dyschondrosteosis (LWD) at the more severe end to SHOX-related short stature at the milder end of the spectrum. Most alterations are whole gene deletions, point mutations within the coding region, or microdeletions in its flanking sequences. Here, we present the clinical and molecular data as well as the potential molecular mechanism underlying a novel microdeletion, causing a variable SHOX-related haploinsufficiency disorder in a three-generation family. The phenotype resembles that of LWD in females, in males, however, the phenotypic expression is milder. The 15523-bp SHOX intragenic deletion, encompassing exons 3-6, was initially detected by array-CGH, followed by MLPA analysis. Sequencing of the breakpoints indicated an Alu recombination-mediated deletion (ARMD) as the potential causative mechanism. |
| Databáze: | OpenAIRE |
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