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Digitotalar dysmorphism: Molecular elucidation

Anna Alvera Vorster, Peter Beighton, Rajkumar Sewcharan Ramesar

Abstract


Dominantly inherited digitotalar dysmorphism (DTD), which is characterised by flexion contractures of digits and ‘rocker-bottom’ feet due to a vertical talus, was first described in a South African family of European stock in 1972. We review the clinical manifestations and document the molecular basis for DTD in this prototype family. This family was restudied in 1995 and 2006 and biological specimens were obtained for molecular studies. Since the distal arthrogryposes (DAs) are genetically heterogeneous, an unbiased approach to mutation identification was undertaken through whole-exome next-generation sequencing of DNA from a single DTD-affected female. Venous blood specimens were obtained for DNA banking and subsequent molecular studies. Analysis of the nine genes that had previously been shown to cause DAs revealed a pathogenic mutation in exon nine of TNNT3. The presence of the p.(Arg63His) missense mutation at position 63 of TNNT3 was confirmed through direct cycle sequencing of genomic DNA in six affected family members for whom DNA had been archived.


Authors' affiliations

Anna Alvera Vorster, MRC Human Genetics Research Unit, Division of Human Genetics, Institute for Infectious Diseases and Molecular Medicine, Department of Clinical Laboratory Sciences, Faculty of Health Sciences, University of Cape Town, South Africa

Peter Beighton, MRC Human Genetics Research Unit, Division of Human Genetics, Institute for Infectious Diseases and Molecular Medicine, Department of Clinical Laboratory Sciences, Faculty of Health Sciences, University of Cape Town, South Africa

Rajkumar Sewcharan Ramesar, MRC Human Genetics Research Unit, Division of Human Genetics, Institute for Infectious Diseases and Molecular Medicine, Department of Clinical Laboratory Sciences, Faculty of Health Sciences, University of Cape Town, South Africa

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Keywords

Digitotalar dysmorphism; Distal arthrogryposis; TNNT3; Vertical talus

Cite this article

South African Medical Journal 2016;106(3):253-255. DOI:10.7196/SAMJ.2016.v106i3.10134

Article History

Date submitted: 2015-09-29
Date published: 2016-02-02

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