Clinical, genetic, and orthopedic characteristics of large group of patients with diastrophic dysplasia
- Authors: Gorodilova D.V.1, Markova T.V.1, Kenis V.M.2,3, Melchenko E.V.2, Akinshina A.D.4, Ogorodova N.Y.1, Shchagina O.A.1, Dadali E.L.1, Kutsev S.I.1
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Affiliations:
- Research Centre for Medical Genetics
- H. Turner National Medical Research Center for Children’s Orthopedics and Trauma Surgery
- North-Western State Medical University named after I.I. Mechnikov
- Priorov Central Institute for Trauma and Orthopedics
- Issue: Vol 12, No 1 (2024)
- Pages: 29-41
- Section: Clinical studies
- Submitted: 26.01.2024
- Accepted: 13.03.2024
- Published: 29.03.2024
- URL: https://journals.eco-vector.com/turner/article/view/626039
- DOI: https://doi.org/10.17816/PTORS626039
- ID: 626039
Cite item
Abstract
BACKGROUND: Diastrophic dysplasia (OMIM #222600) is a rare congenital autosomal recessive skeletal dysplasia associated with homozygous or compound-heterozygous variants in the sulfate transporter gene SLC26A2. Clinical and radiological descriptions of diastrophic dysplasia in patients of different ages will help improve the diagnosis and orthopedic treatment.
AIM: To describe clinical and genetic characteristics of Russian patients with diastrophic dysplasia caused by previously described and newly identified pathogenic SLC26A2 variants.
MATERIALS AND METHODS: A comprehensive examination of 28 Russian patients from 28 unrelated families aged 3 months to 34 years with clinical and radiological signs of diastrophic dysplasia was performed. To confirm the diagnosis, genealogical analysis, clinical examination, radiography, and targeted research of SLC26A2 using direct Sanger sequencing were performed.
RESULTS: Typical clinical and radiological signs sufficient for diagnosing diastrophic dysplasia in newborns have been identified, which included rhizo/mesomelic shortening of the upper and lower extremities, congenital clubfoot, hand anomalies, multiple dislocations, and joint contractures. In our patients, 14 SLC26A2 variants were identified, 9 of which were first discovered. The most common variant identified in Russian patients with diastrophic dysplasia was c.1957T>A (p.Cys653Ser), which accounted for 50% of the alleles.
CONCLUSIONS: Clinical and genetic analyses of Russian patients with diastrophic dysplasia made it possible to identify the core clinical and radiological signs and evaluate the polymorphism of the clinical manifestations of the disease. In contrast to previously examined patients from European populations (including Finland with the largest number of patients with diastrophic dysplasia), 50% of the cases in the Russian population are caused by the c.1957T>A (p.Cys653Ser) homozygous or compound-heterozygous variant.
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About the authors
Darya V. Gorodilova
Research Centre for Medical Genetics
Email: osipova@med-gen.ru
ORCID iD: 0000-0002-5863-3543
SPIN-code: 9835-9616
MD, geneticist
Russian Federation, 1 Moskvorechye str., Moscow, 115522Tatiana V. Markova
Research Centre for Medical Genetics
Email: markova@med-gen.ru
ORCID iD: 0000-0002-2672-6294
SPIN-code: 4707-9184
MD, PhD, Dr. Sci. (Med.)
Russian Federation, 1 Moskvorechye str., Moscow, 115522Vladimir M. Kenis
H. Turner National Medical Research Center for Children’s Orthopedics and Trauma Surgery; North-Western State Medical University named after I.I. Mechnikov
Email: kenis@mail.ru
ORCID iD: 0000-0002-7651-8485
SPIN-code: 5597-8832
http://www.rosturner.ru/kl4.htm
MD, PhD, Dr. Sci. (Med.), Professor
Russian Federation, Saint Petersburg; Saint PetersburgEvgenii V. Melchenko
H. Turner National Medical Research Center for Children’s Orthopedics and Trauma Surgery
Email: emelchenko@gmail.com
ORCID iD: 0000-0003-1139-5573
SPIN-code: 1552-8550
MD, PhD, Cand. Sci. (Med.)
Russian Federation, Saint PetersburgAleksandra D. Akinshina
Priorov Central Institute for Trauma and Orthopedics
Email: akinishna@narod.ru
ORCID iD: 0000-0002-7319-5350
SPIN-code: 8740-6190
MD, PhD, Cand. Sci. (Med.)
Russian Federation, MoscowNatalya Yu. Ogorodova
Research Centre for Medical Genetics
Email: ognatashka@mail.ru
ORCID iD: 0000-0001-6151-5022
SPIN-code: 4300-7904
MD, laboratory geneticist
Russian Federation, 1 Moskvorechye str., Moscow, 115522Olga A. Shchagina
Research Centre for Medical Genetics
Email: schagina@dnalab.ru
ORCID iD: 0000-0003-4905-1303
SPIN-code: 9491-2411
MD, PhD, Dr. Sci. (Med.)
Russian Federation, 1 Moskvorechye str., Moscow, 115522Elena L. Dadali
Research Centre for Medical Genetics
Email: genclinic@yandex.ru
ORCID iD: 0000-0001-5602-2805
SPIN-code: 3747-7880
MD, PhD, Dr. Sci. (Med.), Professor
Russian Federation, 1 Moskvorechye str., Moscow, 115522Sergey I. Kutsev
Research Centre for Medical Genetics
Author for correspondence.
Email: kutsev@mail.ru
ORCID iD: 0000-0002-3133-8018
SPIN-code: 5544-8742
MD, PhD, Dr. Sci. (Med.), Professor, Сorresponding member of the Russian Academy of Sciences
Russian Federation, 1 Moskvorechye str., Moscow, 115522References
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