Osteogenesis Imperfecta: Diagnostic Feature

Ignatovich, Olga; Намазова-Баранова, Л. С.; Маргиева, Т. В.; Яхяева, Г. Т.; Zhurkova, N.V.; Савостьянов, К. В.; Пушков, А. А.; Krotov, I. A.

doi:10.15690/pf.v15i3.1902

Cited by 11 publications

(7 citation statements)

References 85 publications

(94 reference statements)

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“…The classification of the disease, taking into account the molecular pathogenesis of the disease, complicated the work of clinical doctors and in 2016 the International committee of nomenclature of constitutional disorders of the skele ton, INCDS) reduced the classification to 5 forms, retaining 4 types, which were originally described by silence and adding a 5th type. In total, 5 groups of the disease were identified using the Arabic digital system, which indicates the unifying phenotypic characteristics, and individual (characteristic for a particular type) changes still retained their original Roman designation (Table 2) (Ignatovich et al, 2018). This characteristic leaves room for the inclusion of new genes found as the cause of osteogenesis imperfecta until the degree of heterogeneity of the disease is identified.…”

Section: Evolution Of Classification Criteria Of Osteogenesis Imperfectamentioning

confidence: 99%

“…To date, 20 genes responsible for the development of OI have been identified. The autosomal dominant type of ND inheritance in most cases is caused by defects in the COLIA1 or COLIA2 genes of type I collagen chains encoding α1 (I) and α2 (I) peptide type I collagen chains, respectively (Ignatovich et al, 2018). Autosomal dominant disease inheritance options have also been described in several patients with mutations in the IFITM5 (MIM: 614757) and P4HB (MIM: 176790) genes.…”

Section: Modern Views On the Etiology And Pathogenesis Of Osteogenesimentioning

confidence: 99%

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Modern classification and molecular-genetic aspects of osteogenesis imperfecta

Zaripova

Хусаинова

2020

Vestn. VOGiS

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Osteogenesis imperfecta (imperfect osteogenesis in the Russian literature) is the most common hereditary form of bone fragility, it is a genetically and clinically heterogeneous disease with a wide range of clinical severity, often leading to disability from early childhood. It is based on genetic disorders leading to a violation of the structure of bone tissue, which leads to frequent fractures, impaired growth and posture, with the development of characteristic disabling bone deformities and associated problems, including respiratory, neurological, cardiac, renal impairment, hearing loss. Osteogenesis imperfecta occurs in both men and women, the disease is inherited in both autosomal dominant and autosomal recessive types, there are sporadic cases of the disease due to de novomutations, as well as X-linked forms. The term “osteogenesis imperfecta” was coined by W. Vrolick in the 1840s. The first classification of the disease was made in 1979 and has been repeatedly reviewed due to the identification of the molecular cause of the disease and the discovery of new mechanisms for the development of osteogenesis imperfecta. In the early 1980s, mutations in two genes of collagen type I (COL1A1and COL1A2) were first associated with an autosomal dominant inheritance type of osteogenesis imperfecta. Since then, 18 more genes have been identified whose products are involved in the formation and mineralization of bone tissue. The degree of genetic heterogeneity of the disease has not yet been determined, researchers continue to identify new genes involved in its pathogenesis, the number of which has reached 20. In the last decade, it has become known that autosomal recessive, autosomal dominant and X-linked mutations in a wide range of genes, encoding proteins that are involved in the synthesis of type I collagen, its processing, secretion and post-translational modification, as well as in proteins that regulate the differentiation and activity of bone-forming cells, cause imperfect osteogenesis. A large number of causative genes complicated the classical classification of the disease and, due to new advances in the molecular basis of the disease, the classification of the disease is constantly being improved. In this review, we systematized and summarized information on the results of studies in the field of clinical and genetic aspects of osteogenesis imperfecta and reflected the current state of the classification criteria for diagnosing the disease.

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Section: Evolution Of Classification Criteria Of Osteogenesis Imperfectamentioning

confidence: 99%

Section: Modern Views On the Etiology And Pathogenesis Of Osteogenesimentioning

confidence: 99%

Modern classification and molecular-genetic aspects of osteogenesis imperfecta

Zaripova

Хусаинова

2020

Vestn. VOGiS

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“…It has been demonstrated that there is a 25% risk that a child whose parent suffers from bronchial asthma also develop this disease. If both parents have asthma, the risk increases to 50% [ 4 ]. Furthermore, it has been proved that there exists an association between the increasing incidence rate of BA and aggravated soil, air, and water contamination [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

Genetic Variants Associated with Bronchial Asthma Specific to the Population of the Russian Federation

et al. 2023

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Bronchial asthma (BA) is a disease that still lacks an exhaustive treatment protocol. In this regard, the global medical community pays special attention to the genetic prerequisites for the occurrence of this disease. Therefore, the search for the genetic polymorphisms underlying bronchial asthma has expanded considerably. As the present study progressed, a significant amount of scientific medical literature was analyzed and 167 genes reported to be associated with the development of bronchial asthma were identified. A group of participants (n = 7,303) who had voluntarily provided their biomaterial (venous blood) to be used in the research conducted by the Federal Medical Biological Agency of Russia was formed to subsequently perform a bioinformatic verification of known associations and search for new ones. This group of participants was divided into four cohorts, including two sex-distinct cohorts of individuals with a history of asthma and two sex-distinct cohorts of apparently healthy individuals. A search for polymorphisms was made in each cohort among the selected genes, and genetic variants were identified whose difference in occurrence in the different cohorts was statistically significant (significance level less than 0.0001). The study revealed 11 polymorphisms that affect the development of asthma: four genetic variants (rs869106717, rs1461555098, rs189649077, and rs1199362453), which are more common in men with bronchial asthma compared to apparently healthy men; five genetic variants (rs1923038536, rs181066119, rs143247175, rs140597386, and rs762042586), which are more common in women with bronchial asthma compared to apparently healthy women; and two genetic variants (rs1219244986 and rs2291651) that are rare in women with a history of asthma.

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“…It has been demonstrated that a decrease in TNSALP activity and the concentration of its substrates correlate with the severity of the clinical symptoms of HPP, defining a heterogeneous phenotype of the disease [ 8 ]. However, the activity of TNSALP can decrease under the influence of drugs, the lack of zinc, magnesium (in celiac disease), achondroplasia, and anemia and lead to an increase in liver diseases and osteogenesis imperfecta [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

Clinical and Genetic Characteristics of Pediatric Patients with Hypophosphatasia in the Russian Population

Glotov

Savostyanov

Нагорнова

et al. 2022

IJMS

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(1) Hypophosphatasia (HPP) is a rare inherited disease caused by mutations (pathogenic variants) in the ALPL gene which encodes tissue-nonspecific alkaline phosphatase (TNSALP). HPP is characterized by impaired bone mineral metabolism due to the low enzymatic activity of TNSALP. Knowledge about the structure of the gene and the features and functions of various ALPL gene variants, taking into account population specificity, gives an understanding of the hereditary nature of the disease, and contributes to the diagnosis, prevention, and treatment of the disease. The purpose of the study was to describe the spectrum and analyze the functional features of the ALPL gene variants, considering various HPP subtypes and clinical symptoms in Russian children. (2) From 2014–2021, the study included the blood samples obtained from 1612 patients with reduced alkaline phosphatase activity. The patients underwent an examination with an assessment of their clinical symptoms and biochemical levels of TNSALP. DNA was isolated from dried blood spots (DBSs) or blood from the patients to search for mutations in the exons of the ALPL gene using Sanger sequencing. The PCR products were sequenced using a reagent BigDye Terminator 3.1 kit (Applied Biosystems). Statistical analysis was performed using the GraphPad Prism 8.01 software. (3) The most common clinical symptoms in Russian patients with HPP and two of its variants (n = 22) were bone disorders (75%), hypomyotonia (50%), and respiratory failure (50%). The heterozygous carriage of the causal variants of the ALPL gene was detected in 225 patients. A total of 2 variants were found in 27 patients. In this group (n = 27), we identified 28 unique variants of the ALPL gene, of which 75.0% were missense, 17.9% were frameshift, 3.6% were splicing variants, and 3.6% were duplications. A total of 39.3% (11/28) of the variants were pathogenic, with two variants being probably pathogenic, and 15 variants had unknown clinical significance (VUS). Among the VUS group, 28.6% of the variants (7/28) were discovered by us for the first time. The most common variants were c.571G > A (p.Glu191Lys) and c.1171del (Arg391Valfs*12), with frequencies of 48.2% (13/28) and 11% (3/28), respectively. It was found that the frequency of nonsense variants of the ALPL gene was higher (p < 0.0001) in patients with the perinatal form compared to the infantile and childhood forms of HPP. Additionally, the number of homozygotes in patients with the perinatal form exceeded (p < 0.01) the frequencies of these genotypes in children with infantile and childhood forms of HPP. On the contrary, the frequencies of the compound-heterozygous and heterozygous genotypes were higher (p < 0.01) in patients with infantile childhood HPP than in perinatal HPP. In the perinatal form, residual TNSALP activity was lower (p < 0.0005) in comparison to the infantile and childhood (p < 0.05) forms of HPP. At the same time, patients with the heterozygous and compound-heterozygous genotypes (mainly missense variants) of the ALPL gene had greater residual activity (of the TNSALP protein) regarding those homozygous patients who were carriers of the nonsense variants (deletions and duplications) of the ALPL gene. Residual TNSALP activity was lower (p < 0.0001) in patients with pathogenic variants encoding the amino acids from the active site and the calcium and crown domains in comparison with the nonspecific region of the protein.

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Osteogenesis Imperfecta: Diagnostic Feature

Cited by 11 publications

References 85 publications

Modern classification and molecular-genetic aspects of osteogenesis imperfecta

Modern classification and molecular-genetic aspects of osteogenesis imperfecta

Genetic Variants Associated with Bronchial Asthma Specific to the Population of the Russian Federation

Clinical and Genetic Characteristics of Pediatric Patients with Hypophosphatasia in the Russian Population

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