Clinical and molecular genetic study of genetic skeletal disorders in children

CHENG Sheng-quan

doi:10.11852/zgetbjzz2022-0954

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Chinese Journal of Child Health Care ›› 2022, Vol. 30 ›› Issue (9) : 933-940. DOI: 10.11852/zgetbjzz2022-0954

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Clinical and molecular genetic study of genetic skeletal disorders in children

CHENG Sheng-quan

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Abstract

Genetic skeletal disorders are a group of extremely complex diseases that affect bone development. They can occur in any period from fetal to adult. A total of 461 different skeletal diseases are classified into 42 groups based on clinical, radiographic, and/or molecular phenotypes by the Nosology Committee of the International Skeletal Dysplasia Society in 2019.Pathogenic variants affecting 437 different genes have been found in these disorders. Achondroplasia is the most common genetic bone disease with asymmetrical short stature as the main manifestation, and FGFR3 is its main causal gene. Mucopolysaccharidosis is a group of lysosomal storage diseases caused by the complete degradation of acidic mucopolysaccharides due to enzyme defects. According to the enzyme defects, it can be divided into 7 types. In addition to causing multiplex dysostosis, such diseases often involve multiple systems and organs. Osteogenesis imperfecta and Hypophosphatasia are hereditary bone diseases that affect bone mineral density in children. The former is divided intoⅠto ⅩⅥ types according to genotype and clinical manifestations, and the latter is caused by tissue nonspecific alkaline phosphatase (TNSALP) gene mutation. Pseudoachondroplasia is a genetic bone disease characterized by Multiple epiphyseal dysplasia and short stature. Heterozygous mutations in the cartilage oligomeric protein gene are the only reported pathogenic genes related to its occurrence. Chondrodysplasia punctata is characterized by irregular calcium deposition of epiphyseal cartilage, and it is divided into 5 types according to the inheritance patterns and the severity of clinical phenotype.In a word, the overall incidence of hereditary/genetic skeletal disorders is not low. Due to the extensive development of molecular genetic testing methods, novel pathogenic genetic variants are still being discovered. Only through the profound study of such diseases can new gene therapeutics be found. Yet much more work remains to be done.

Key words

genetic skeletal / achondroplasia / mucopolysaccharidosis / osteogenesis imperfecta / hypophosphatasia / pseudoachondroplasia / chondrodysplasia punctata

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CHENG Sheng-quan. Clinical and molecular genetic study of genetic skeletal disorders in children[J]. Chinese Journal of Child Health Care. 2022, 30(9): 933-940 https://doi.org/10.11852/zgetbjzz2022-0954

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