Journal article

Pseudodiastrophic dysplasia expands the known phenotypic spectrum of defects in proteoglycan biosynthesis

Alicia B Byrne, Shuji Mizumoto, Peer Arts, Patrick Yap, Jinghua Feng, Andreas W Schreiber, Milena Babic, Sarah L King-Smith, Christopher P Barnett, Lynette Moore, Kazuyuki Sugahara, Hatice Mutlu-Albayrak, Gen Nishimura, Jan E Liebelt, Shuhei Yamada, Ravi Savarirayan, Hamish S Scott

Journal of Medical Genetics | BMJ PUBLISHING GROUP | Published : 2020

Abstract

BACKGROUND: Pseudodiastrophic dysplasia (PDD) is a severe skeletal dysplasia associated with prenatal manifestation and early lethality. Clinically, PDD is classified as a 'dysplasia with multiple joint dislocations'; however, the molecular aetiology of the disorder is currently unknown. METHODS: Whole exome sequencing (WES) was performed on three patients from two unrelated families, clinically diagnosed with PDD, in order to identify the underlying genetic cause. The functional effects of the identified variants were characterised using primary cells and human cell-based overexpression assays. RESULTS: WES resulted in the identification of biallelic variants in the established skeletal dys..

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Grants

Awarded by NHMRC


Awarded by Australian Genomic Health Alliance NHMRC Targeted Call for Research into Preparing Australia for the Genomics Revolution in Healthcare


Awarded by Japan Society for the Promotion of Science


Funding Acknowledgements

This research was supported by the NHMRC (APP1123341) and the Australian Genomic Health Alliance NHMRC Targeted Call for Research into Preparing Australia for the Genomics Revolution in Healthcare (GNT1113531) to HSS and CPB; the Australian Cancer Research Foundation to HSS; Grant-in-A id for the Research Center for Pathogenesis of Intractable Diseases from the Research Institute of Meijo University to SM and SY; and Grant-in-A id for Scientific Research (C) 19K07054 from the Japan Society for the Promotion of Science to SM. Additional support was provided by Cancer Council SA's Beat Cancer Project on behalf of its donors and the State Government of South Australia through the Department of Health, and NHMRC Fellowship (APP1023059) to HSS; the Australian Government Research Training Program Scholarship and the Australian Genomics Health Alliance PhD Award and NHMRC (GNT1113531) to ABB; the Takeda Science Foundation to SM; and The Hospital Research Foundation Fellowship to PA.