Natural history and genetic spectrum of the Turkish metaphyseal dysplasia cohort, including rare types caused by biallelic COL10A1, COL2A1, and LBR variants.

Autor: Tüysüz B; Department of Pediatric Genetics, Istanbul University-Cerrahpasa, Cerrahpasa Medical Faculty, Istanbul, Turkey. Electronic address: beyhan@istanbul.edu.tr., Kasap B; Department of Pediatric Genetics, Istanbul University-Cerrahpasa, Cerrahpasa Medical Faculty, Istanbul, Turkey; Department of Genetics, Istanbul University, Aziz Sancar Institute of Experimental Medicine, Istanbul, Turkey., Sarıtaş M; Department of Pediatric Genetics, Istanbul University-Cerrahpasa, Cerrahpasa Medical Faculty, Istanbul, Turkey; Department of Genetics, Istanbul University, Aziz Sancar Institute of Experimental Medicine, Istanbul, Turkey., Alkaya DU; Department of Pediatric Genetics, Istanbul University-Cerrahpasa, Cerrahpasa Medical Faculty, Istanbul, Turkey., Bozlak S; Department of Pediatric Genetics, Istanbul University-Cerrahpasa, Cerrahpasa Medical Faculty, Istanbul, Turkey., Kıykım A; Department of Pediatric Immunology and Allergy, Istanbul University-Cerrahpasa, Cerrahpasa Medical Faculty, Istanbul, Turkey., Durmaz A; Department of Medical Genetics, Faculty of Medicine, Ege University, Izmir, Turkey., Yıldırım T; Department of Orthopedics and Traumatology, University of Health Sciences Turkey, Baltalimani Bone Diseases Training and Research Center, Istanbul, Turkey., Akpınar E; Department of Orthopedics and Traumatology, University of Health Sciences Turkey, Baltalimani Bone Diseases Training and Research Center, Istanbul, Turkey., Apak H; Department of Pediatric Hematology, Istanbul University-Cerrahpasa, Cerrahpasa Medical Faculty, Istanbul, Turkey., Vural M; Department of Neonatology, Istanbul University-Cerrahpasa, Cerrahpasa Medical Faculty, Istanbul, Turkey.
Jazyk: angličtina
Zdroj: Bone [Bone] 2023 Feb; Vol. 167, pp. 116614. Date of Electronic Publication: 2022 Nov 15.
DOI: 10.1016/j.bone.2022.116614
Abstrakt: Background: Metaphyseal chondrodysplasias are a heterogeneous group of diseases characterized by short and bowed long bones and metaphyseal abnormality. The aim of this study is to investigate the genetic etiology and prognostic findings in patients with metaphyseal dysplasia.
Methods: Twenty-four Turkish patients were included in this study and 13 of them were followed for 2-21 years. COL10A1, RMRP sequencing and whole exome sequencing were performed.
Results: Results: Seven heterozygous pathogenic variants in COL10A1 were detected in 17 patients with Schmid type metaphyseal chondrodysplasia(MCDS). The phenotype was more severe in patients with heterozygous missense variants (one in signal peptide domain at the N-terminus of the protein, the other, class-1 group mutation at NC1 domain) compared to the patients with truncating variants. Short stature and coxa vara deformity appeared after 3 and 5 years of age, respectively, while large femoral head resolved after the age of 13 years in MCDS group. Interestingly, one patient with severe phenotype also had a biallelic missense variant in NC1 domain of COL10A1. Three patients with biallelic mutations in RMRP had prenatal onset short stature with short limb, and typical findings of cartilage hair hypoplasia (CHH). While immunodeficiency or recurrent infections were not observed, resistant congenital anemia was detected in one. Biallelic mutation in LBR was described in a patient with prenatal onset short stature, short and curved limb and metaphyseal abnormalities. Unlike previously reported patients, this patient had ectodermal findings, similar to CHH. A biallelic COL2A1 mutation was also found in the patient with lower limb deformities and metaphyseal involvement without vertebral and epiphyseal changes.
Conclusion: Long-term clinical characteristics are presented in a metaphyseal dysplasia cohort, including rare types caused by biallelic COL10A1, COL2A1, and LBR variants. We also point out that the domains where mutations on COL10A1 take place are important in the genotype-phenotype relationship.
Competing Interests: Declaration of competing interest The authors declare no competing interests. The study was approved by the local ethical committee (no: 53721, 07.04.2020).
(Copyright © 2022 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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