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. 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.

Clinical and radiographic characteristics of pycnodysostosis: A systematic review

“…Obtuse mandibular angle, a key diagnostic feature that distinguishes PYCD from cleidocranial dysplasia, was observed in 84.3% of the present sample. This observation supports the findings of Sayed Amr et al, 13 Doherty et al, 7 Markova et al, 49 Sait et al, 4 and Verma and Singh. 87 …”

“…Based on examination of the full texts of these papers, 84 studies 3 4 5 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 ...…”

“…Previous research has underscored the high rate of consanguinity among the parents of individuals diagnosed with PYCD, consistent with the autosomal recessive inheritance pattern of the disease. 4 13 37 49 72 87 …”

Pyknodysostosis: A case report of an 8-year-old male with a rare genetic disorder

“…Pyknodysostosis is an extremely rare genetic disorder characterized by a variety of skeletal abnormalities and potential associated complications. Affected individuals exhibit a unique set of physical characteristics, including short stature, an atypical skull shape, delayed closure of fontanelles, a prominent forehead, and an underdeveloped mid-face with a beaked nose [ 8 ]. Dental anomalies are also frequently observed, such as delayed eruption and retention of primary teeth, hypoplastic enamel, and an increased susceptibility to caries.…”

Detection of respiratory pathogenic bacterial nucleic acid detection by Loop-mediated Isothermal Amplification in patients with bacterial pulmonary infections

“…Currently, the main pathogens of respiratory tract infections include bacteria, viruses, mycoplasma and chlamydia, for example, Klebsiella pneumoniae , Streptococcus pneumoniae , novel coronavirus, respiratory syncytial virus, and Mycoplasma pneumoniae [ 4 , [6] , [7] , [8] ]. Due to genetic variation of the pathogen, one pathogen may lead to different clinical symptoms, and different pathogens may lead to similar clinical manifestations [ 9 , 10 ]. Therefore, empirical administration of drugs based only on the clinical manifestations of patients may lead to clinical treatment failure and can cause an increase in pathogen resistance in the clinic.…”