SFEBES2022 Poster Presentations Neuroendocrinology and Pituitary (72 abstracts)
Identifying and characterising variants in patients with pachydermoperiostosis
Ishita Angurala 1 , Sayka Barry 1 , Tom Rice 1 , Kesson Magid 1 , Ashutosh Rai 1 , Paul Benjamin Loughrey 1,2 , Pinaki Dutta 3 , Maria Stelmachowska Banaś 4 & Márta Korbonits 1
1Center for Endocrinology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom; 2Patrick G Johnston Centre for Cancer Research, Queen’s University, Belfast, United Kingdom; 3Department of Endocrinology, Nehru Hospital Extension, Postgraduate Institute of Medical Education and Research, Chandigarh, India; 4Klinika Endokrynologii, Centrum Medycznego Kształcenia Podyplomowego, Warszawa, Poland
Introduction: Pachydermoperiostosis (primary hypertrophic osteoarthropathy, PHOA) is a rare genetic condition characterised by digital clubbing, pachydermia, hyperhidrosis, cutis verticis gyrata and periostosis. The SLCO2A1 transporter and HPGD enzyme genes play an important role in prostaglandin metabolism, hence loss of function mutations in them causes PHOA. To date, according to the VarSome database 101 and 41 variants have been identified in the SLCO2A1 and HPGD genes respectively. The signs and symptoms of PHOA can be confused or overlap with some conditions like acromegaly, thyroid acropachy, psoriatic/rheumatoid arthritis and secondary hypertrophic osteoarthrpathy. Although certain symptoms can help differentiate from these other conditions, they are not always apparent due to the variable penetrance of PHOA. Hence it is important to identify known or novel variants in patients.
Aim: The aim of this project is to examine both disease-causing genes (HPGD and SLCO2A1) in PHOA patients to identify and characterise known and novel variants.
Methods: Performed Sanger Sequencing for HPGD (seven exons) and SLCO2A1 (14 exons) on peripheral blood DNA. The identified variants on both genes were classified using the American College of Medical Genetics (ACMG) classification guidelines that combine a series of functional, genetic, population and in silico evidence and calculating their strength.
Results and discussion: We identified a total of 14 variants in 14 patients or family members of probands. Six of the 14 variants were novel. The novel variant in the HPGD gene was g.30009_30012delGTAA. Novel variants in the SLCO2A1 gene were: c.822_823insA (p.Phe275IlefsTer21), c.724_725insCCTGCCAC, c.161G>A (p.Ser54Asn), c.165C>G (p.Ser55Arg) and c.1604C>G (p Pro535Arg). Our in-silico analysis of these variants including protein properties and functional outcomes suggest a likely pathogenic or pathogenic effect. These findings could further the genotype database for PHOA, and the genotype-phenotype correlations can provide insights to clinicians and help future genetic diagnosis and counselling.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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