Mesomelic dysplasia Kantaputra type (MDK) is characterized by marked mesomelic shortening of the upper and lower limbs originally described in a Thai family. To identify the cause of MDK, we performed array CGH and identified two microduplications on chromosome 2 (2q31.1-q31.2) encompassing ∼481 and 507 kb, separated by a segment of normal copy number. The more centromeric duplication encompasses the entire HOXD cluster, as well as the neighboring genes EVX2 and MTX2. The breakpoints of the duplication localize to the same region as the previously identified inversion of the mouse mutant ulnaless (Ul), which has a similar phenotype as MDK. We propose that MDK is caused by duplications that modify the topography of the locus and as such result in deregulation of HOXD gene expression.
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http://dx.doi.org/10.1038/ejhg.2010.116 | DOI Listing |
Hum Genome Var
December 2024
Department of Genetic Counseling, Asahikawa Medical University Hospital, 2-1-1-1 Midorigaoka-Higashi, Asahikawa, Hokkaido, Japan.
We report a case of a fetus with short-rib thoracic dysplasia (SRTD) with polydactyly that also presented with atypical severe acro-mesomelic ossification defects. Genetic analysis using massively parallel sequencing of a skeletal dysplasia panel revealed compound heterozygous variants in DYNC2H1. This clinical report highlights the challenges associated with diagnosing the diverse phenotypes in the SRTD group and emphasizes the importance of genetic surveillance with a targeted gene panel for accurate diagnosis.
View Article and Find Full Text PDFJ Orthop Case Rep
July 2024
Department of Orthopaedics, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India.
Introduction: Neglected bilateral clubfoot clubhand deformity is a mesomelic type of dysplasia that is characterized by disproportionate shortness of the middle segment of all limbs and is a form of short-limb dwarfism. Affected individuals are clinically of normal stature with particularly short mesomelic segments with nearly symmetric limb abnormalities.
Case Report: The patient was a 20-year-old male Indian who came to outpatient department for cosmetic purpose.
Eur J Hum Genet
June 2024
Shriners Hospital for Children, Montreal, QC, Canada.
Haploinsufficiency of the short stature homeobox-containing (SHOX) gene leads to a phenotypic spectrum ranging from Leri-Weill dyschondrosteosis (LWD) to SHOX-deficient short stature. SHOX nullizygosity leads to Langer mesomelic dysplasia. Pathogenic variants can include whole or partial gene deletions or duplications, point mutations within the coding sequence, and deletions of upstream and downstream regulatory elements.
View Article and Find Full Text PDFGenome Med
May 2024
Center for Integrative Genomics, University of Lausanne, Genopode Building, Lausanne, CH, 1015, Switzerland.
Am J Hum Genet
June 2024
Oxford Biomedical Research Centre, Centre for Human Genetics, University of Oxford, Oxford, UK. Electronic address:
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