Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/11901
Title: Mutations in SH3PXD2B cause Borrone dermato-cardio-skeletal syndrome.
Austin Authors: Wilson, Gabrielle R;Sunley, Jasmine;Smith, Katherine R;Pope, Kate;Bromhead, Catherine J;Fitzpatrick, Elizabeth;Di Rocco, Maja;van Steensel, Maurice;Coman, David J;Leventer, Richard J;Delatycki, Martin B ;Amor, David John;Bahlo, Melanie;Lockhart, Paul J
Affiliation: Department of Metabolic Medicine, The Royal Children's Hospital, Brisbane, QLD, Australia
Bruce Lefroy Centre for Genetic Health Research, Murdoch Childrens Research Institute, The Royal Children's Hospital, Flemington Road, Melbourne, Victoria, Australia
Bioinformatics Division, The Walter and Eliza Hall Institute, Melbourne, Victoria, Australia
Department of Medical Biology, The University of Melbourne, Melbourne, VIC, Australia
Department of Mathematics and Statistics, The University of Melbourne, Melbourne, VIC, Australia
Murdoch Childrens Research Institute, Royal Children's Hospital, Melbourne, VIC, Australia
Department of Neurology, Royal Children's Hospital, Melbourne, VIC, Australia
Department of Clinical Genetics, Austin Health, Heidelberg, VIC, Australia
Bioinformatics Division, The Walter and Eliza Hall Institute, Melbourne, VIC, Australia
Bruce Lefroy Centre for Genetic Health Research, Murdoch Childrens Research Institute, The Royal Children's Hospital, Flemington Road, Melbourne, VIC, Australia
Department of Paediatrics, The University of Melbourne, Melbourne, VIC, Australia
Unit of Rare Diseases, Department of Pediatrics, Istituto Giannina Gaslini, Genoa, Italy.
Department of Dermatology, Maastricht University Medical Center, Maastricht, The Netherlands.
Issue Date: 9-Oct-2013
Publication information: European Journal of Human Genetics : Ejhg 2013; 22(6): 741-7
Abstract: Borrone Dermato-Cardio-Skeletal (BDCS) syndrome is a severe progressive autosomal recessive disorder characterized by coarse facies, thick skin, acne conglobata, dysmorphic facies, vertebral abnormalities and mitral valve prolapse. We identified a consanguineous kindred with a child clinically diagnosed with BDCS. Linkage analysis of this family (BDCS1) identified five regions homozygous by descent with a maximum LOD score of 1.75. Linkage analysis of the family that originally defined BDCS (BDCS3) identified an overlapping linkage peak at chromosome 5q35.1. Sequence analysis identified two different homozygous mutations in BDCS1 and BDCS3, affecting the gene encoding the protein SH3 and PX domains 2B (SH3PXD2B), which localizes to 5q35.1. Western blot analysis of patient fibroblasts derived from affected individuals in both families demonstrated complete loss of SH3PXD2B. Homozygosity mapping and sequence analysis in a second published BDCS family (BDCS2) excluded SH3PXD2B. SH3PXD2B is required for the formation of functional podosomes, and loss-of-function mutations in SH3PXD2B have recently been shown to underlie 7 of 13 families with Frank-Ter Haar syndrome (FTHS). FTHS and BDCS share some overlapping clinical features; therefore, our results demonstrate that a proportion of BDCS and FTHS cases are allelic. Mutations in other gene(s) functioning in podosome formation and regulation are likely to underlie the SH3PXD2B-mutation-negative BDSC/FTHS patients.
Gov't Doc #: 24105366
URI: http://ahro.austin.org.au/austinjspui/handle/1/11901
DOI: 10.1038/ejhg.2013.229
URL: https://pubmed.ncbi.nlm.nih.gov/24105366
Type: Journal Article
Subjects: Abnormalities, Multiple.genetics.pathology
Adaptor Proteins, Signal Transducing.genetics
Consanguinity
Craniofacial Abnormalities.pathology
Female
Humans
Limb Deformities, Congenital.pathology
Male
Mitral Valve Prolapse.pathology
Mutation
Pedigree
Skin Abnormalities.pathology
Syndrome
Appears in Collections:Journal articles

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