Clinical and genetic characterization of three Russian patients with pycnodysostosis due to pathogenic variants in the CTSK gene
Abstract Background Pycnodysostosis (PD, OMIM # 265800) is a rare variant of skeletal dysplasia with an autosomal recessive type of inheritance, characterized by a combination of specific features such as disproportionate nanism, generalized osteosclerosis, and distinct craniofacial dysmorphism. Rad...
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| Format: | Article |
| Language: | English |
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Wiley
2022-05-01
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| Series: | Molecular Genetics & Genomic Medicine |
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| Online Access: | https://doi.org/10.1002/mgg3.1904 |
| _version_ | 1811288071546601472 |
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| author | Tatiana Vladimirovna Markova Vladimir Kenis Evgeniy Melchenko Darya Guseva Darya Osipova Nailya Galeeva Tatiana Nagornova Elena Leonidovna Dadali |
| author_facet | Tatiana Vladimirovna Markova Vladimir Kenis Evgeniy Melchenko Darya Guseva Darya Osipova Nailya Galeeva Tatiana Nagornova Elena Leonidovna Dadali |
| author_sort | Tatiana Vladimirovna Markova |
| collection | DOAJ |
| description | Abstract Background Pycnodysostosis (PD, OMIM # 265800) is a rare variant of skeletal dysplasia with an autosomal recessive type of inheritance, characterized by a combination of specific features such as disproportionate nanism, generalized osteosclerosis, and distinct craniofacial dysmorphism. Radiographic features include acro‐osteolysis of the distal phalanges in association with sclerosing bone lesions with multiple fractures. The polymorphism of the clinical manifestations of pycnodysostosis and low prevalence of the disorder lead to the difficulties with early. Methods The following tests were used for diagnostics: genealogical analysis, clinical examination, neurological examination according to the standard method with an assessment of the psychoemotional sphere, radiological analysis, searching for pathogenic variants in the CTSK gene by the automated Sanger sequencing. Results We describe first clinical and genetic characteristics of three Russian patients with pycnodysostosis from unrelated families. Two patients have a novel homozygous nucleotide substitution c.746T>A (p. Ile249Asn), and one has a previously described homozygous pathogenic variant c.746T>C (p.Ile249Thr) in the CTSK gene. In all three cases, a transition or transversion was found at nucleotide position 746 in exon 6 of the CTSK gene, leading to two different amino acid substitutions in the polypeptide chain. The obtained results may indicate the presence of a major pathogenic variant in the CTSK gene, leading to the typical manifestation of the disease. Conclusion The data presented in the study enlarge the clinical, radiological, and mutational spectrum of pycnodysostosis. Typical clinical manifestations and the small size of the CTSK gene make the automated Sanger sequencing the optimal method for diagnosis of pycnodysostosis. |
| first_indexed | 2024-04-13T03:29:33Z |
| format | Article |
| id | doaj.art-71f283ca354a423ea46e1fbf40530c03 |
| institution | Directory Open Access Journal |
| issn | 2324-9269 |
| language | English |
| last_indexed | 2024-04-13T03:29:33Z |
| publishDate | 2022-05-01 |
| publisher | Wiley |
| record_format | Article |
| series | Molecular Genetics & Genomic Medicine |
| spelling | doaj.art-71f283ca354a423ea46e1fbf40530c032022-12-22T03:04:32ZengWileyMolecular Genetics & Genomic Medicine2324-92692022-05-01105n/an/a10.1002/mgg3.1904Clinical and genetic characterization of three Russian patients with pycnodysostosis due to pathogenic variants in the CTSK geneTatiana Vladimirovna Markova0Vladimir Kenis1Evgeniy Melchenko2Darya Guseva3Darya Osipova4Nailya Galeeva5Tatiana Nagornova6Elena Leonidovna Dadali7Research Centre for Medical Genetics Moscow RussiaH.Turner National Medical Research Center for Сhildren's Orthopedics and Trauma Surgery Pushkin RussiaH.Turner National Medical Research Center for Сhildren's Orthopedics and Trauma Surgery Pushkin RussiaResearch Centre for Medical Genetics Moscow RussiaResearch Centre for Medical Genetics Moscow RussiaResearch Centre for Medical Genetics Moscow RussiaResearch Centre for Medical Genetics Moscow RussiaResearch Centre for Medical Genetics Moscow RussiaAbstract Background Pycnodysostosis (PD, OMIM # 265800) is a rare variant of skeletal dysplasia with an autosomal recessive type of inheritance, characterized by a combination of specific features such as disproportionate nanism, generalized osteosclerosis, and distinct craniofacial dysmorphism. Radiographic features include acro‐osteolysis of the distal phalanges in association with sclerosing bone lesions with multiple fractures. The polymorphism of the clinical manifestations of pycnodysostosis and low prevalence of the disorder lead to the difficulties with early. Methods The following tests were used for diagnostics: genealogical analysis, clinical examination, neurological examination according to the standard method with an assessment of the psychoemotional sphere, radiological analysis, searching for pathogenic variants in the CTSK gene by the automated Sanger sequencing. Results We describe first clinical and genetic characteristics of three Russian patients with pycnodysostosis from unrelated families. Two patients have a novel homozygous nucleotide substitution c.746T>A (p. Ile249Asn), and one has a previously described homozygous pathogenic variant c.746T>C (p.Ile249Thr) in the CTSK gene. In all three cases, a transition or transversion was found at nucleotide position 746 in exon 6 of the CTSK gene, leading to two different amino acid substitutions in the polypeptide chain. The obtained results may indicate the presence of a major pathogenic variant in the CTSK gene, leading to the typical manifestation of the disease. Conclusion The data presented in the study enlarge the clinical, radiological, and mutational spectrum of pycnodysostosis. Typical clinical manifestations and the small size of the CTSK gene make the automated Sanger sequencing the optimal method for diagnosis of pycnodysostosis.https://doi.org/10.1002/mgg3.1904CTSK genepycnodysostosisskeletal dysplasia |
| spellingShingle | Tatiana Vladimirovna Markova Vladimir Kenis Evgeniy Melchenko Darya Guseva Darya Osipova Nailya Galeeva Tatiana Nagornova Elena Leonidovna Dadali Clinical and genetic characterization of three Russian patients with pycnodysostosis due to pathogenic variants in the CTSK gene Molecular Genetics & Genomic Medicine CTSK gene pycnodysostosis skeletal dysplasia |
| title | Clinical and genetic characterization of three Russian patients with pycnodysostosis due to pathogenic variants in the CTSK gene |
| title_full | Clinical and genetic characterization of three Russian patients with pycnodysostosis due to pathogenic variants in the CTSK gene |
| title_fullStr | Clinical and genetic characterization of three Russian patients with pycnodysostosis due to pathogenic variants in the CTSK gene |
| title_full_unstemmed | Clinical and genetic characterization of three Russian patients with pycnodysostosis due to pathogenic variants in the CTSK gene |
| title_short | Clinical and genetic characterization of three Russian patients with pycnodysostosis due to pathogenic variants in the CTSK gene |
| title_sort | clinical and genetic characterization of three russian patients with pycnodysostosis due to pathogenic variants in the ctsk gene |
| topic | CTSK gene pycnodysostosis skeletal dysplasia |
| url | https://doi.org/10.1002/mgg3.1904 |
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