Please use this identifier to cite or link to this item: https://repository.monashhealth.org/monashhealthjspui/handle/1/36725
Conference/Presentation Title: The Australian autoinflammatory diseases registry (AADRY): A streamlined approach to the genetic and immunological evaluation of monogenic autoinflammatory diseases.
Authors: Cains G.;Munro J.;Ojaimi S. ;Renton W.;Singh-Grewal D.;Slade C.;Smart J.;Tiller G.;Whitehead B.;Woods J.;Wu P.;Mehr S.;Wicks I.P.;Masters S.L.;Moghaddas F.;Harris J.;Vekic D.;Cassandra H.;Calleja D.J.;Adib N.;Akikusa J.;Allen R.;Andrews D.;Bryant V.;Chaitow J.;Christensen B.;Coman D.;Cook M.;Cox A.;Douglass J.A.;Gowdie P. ;Hosking L.;Hunter M.F. ;Kubler P.;Lee S.J.
Monash Health Department(s): Genetics
Paediatric - Rheumatology
Institution: (Moghaddas, Douglass, Slade) Clinical Immunology and Allergy, Royal Melbourne Hospital, Red Hill, Australia (Moghaddas, Harris, Cassandra, Calleja, Wicks, Masters) Inflammation Division, WEHI, Red Hill, Australia (Moghaddas, Bryant, Slade, Wicks, Masters) Department of Medical Biology, University of Melbourne, Red Hill, Australia (Vekic, Cains, Woods) Dermatology Department, Liverpool Hospital, Red Hill, Australia (Adib) Queensland Rheumatology Services, Arthur House, Red Hill, Australia (Akikusa, Allen, Cox, Gowdie, Munro, Renton, Tiller) Rheumatology Department, Royal Children's Hospital, Canberra, Australia (Andrews) John Curtin School of Medical Research, Australian National University, Canberra, Australia (Bryant, Slade) Immunology Division, WEHI, Brisbane, Australia (Chaitow, Singh-Grewal) Rheumatology Department, Children's Hospital at Westmead, Brisbane, Australia (Christensen) Gastroenterology Department, Royal Melbourne Hospital, Brisbane, Australia (Coman) Metabolic Medicine, Queensland Children's Hospital, Brisbane, Australia (Cook) Centre for Personalised Immunology, Brisbane, Australia (Cox, Gowdie) Paediatric Rheumatology Department, Monash Children's Hospital, Brisbane, Australia (Hosking, Smart, Mehr) Paediatric Immunology Department, Royal Children's Hospital, Brisbane, Australia (Hunter) Monash Genetics, Monash Health, Brisbane, Australia (Kubler) Department of Rheumatology, Royal Brisbane and Women's Hospital, Brisbane, Australia (Lee) Department of Rheumatology, Perth Children's Hospital, Brisbane, Australia (Ojaimi) Department of Infection and Immunity, Monash Children's Hospital, Brisbane, Australia (Singh-Grewal) Rheumatology Department, Sydney Children's Hospital, Brisbane, Australia (Whitehead) Rheumatology Department, Queensland Children's Hospital, Brisbane, Australia (Wu) Australian Phenomics Facility, Australian National University, Canberra, Australia (Wicks) Rheumatology Department, Royal Melbourne Hospital, Australia
Presentation/Conference Date: 10-Jun-2019
Copyright year: 2019
Publisher: BioMed Central Ltd.
Publication information: Pediatric Rheumatology. Conference: 10th Congress of International Society of Systemic Auto-Inflammatory Diseases, ISSAID 2019. Genoa Italy. 17 (Supplement 1) (no pagination), 2019. Date of Publication: May 2019.
Abstract: Introduction: Since the original publication in 1971 outlining two cases of FMF complicated by pulmonary amyloidosis, there have been only two studies looking at the status of monogenic autoinflammatory disorders (AIDs) in Australia. Clinicians caring for patients with an AID without a pathogenic mutation in known diseasecausing genes do not have a streamlined approach to further genetic evaluation. Objective(s): The Australian Autoinflammatory Diseases Registry (AADRY) aims to provide clinicians with access to a research team to further evaluate patients without an established genetic diagnosis as well as to address limitations in the current knowledge of AIDs in Australia. Method(s): Patients with suspected AIDs were recruited as trios. Whole exome sequencing (WES) was performed on whole blood or saliva using the Hiseq 4000 platform and Illumina Sureselect XT V5 library. A variant list was generated using a pipeline, variant caller and filtering strategy previously described. Initial filtering of the variants proceeded by excluding synonymous and common variants, and intronic variants more than 50 base pairs from an intron-exon junction. Sequence data quality was assessed by viewing the BAM file on the Integrated genomics viewer. Variant classification was based on ACMG consensus guidelines. Result(s): From September 2015 to June 2018, 34 index cases underwent WES. Initial curation analysis looked at autoinflammatory genes as per IUIS and ISSAID. A total of 77 variants in 34 patients were filtered with no pathogenic or likely pathogenic variants detected. The majority (82%) of variants were VUS. Nineteen trios underwent WES. Seventy-one de novo variants (mean 4 per index case), 77 AR variants (mean 4) and 253 potential CH variants (mean 13) were curated. Of the 5 families recruited with more than one symptomatic member, a likely pathogenic variant segregating with disease was found in one family. The pedigree demonstrated multiple generations symptomatic of various degrees of pustular acne and hidradenitis suppurtiva. A novel truncating variant in NCSTN (c.1485C>T) encoding nicastrin p.Glu454X segregated with disease. Conclusion(s): AADRY has curated the WES of 34 index cases, including 19 trios. A likely pathogenic variant was discovered in one family with a highly penetrant dominantly inherited dermatological phenotype. No clear genetic diagnosis has been made in the remaining index cases, however a number of candidate novel variants are being evaluated. Further work is now underway to gather data on patients with genetically defined AIDs so that the retrospective cohort of patients with an established diagnosis is captured.
Conference Start Date: 2019-03-31
Conference End Date: 2019-04-03
DOI: http://monash.idm.oclc.org/login?url=http://dx.doi.org/10.1186/s12969-019-0313-x
ISSN: 1546-0096
URI: https://repository.monashhealth.org/monashhealthjspui/handle/1/36725
Type: Conference Abstract
Type of Clinical Study or Trial: Observational study (cohort, case-control, cross sectional or survey)
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