A Severe Case of Spondylometaphyseal Dysplasia Algerian Type with Two Mutations in COL2A1

Abstract

Spondylometaphyseal dysplasia Algerian type (MIM no.: 184253) is an uncommon autosomal dominant skeletal dysplasia caused by heterozygous mutations in the COL2A1 gene (MIM no.: 120140). In this case based review, we reported a 5-year-old boy with short stature, severe dorsolumbar scoliosis, lumbar hyperlordosis, short trunk, and severe genu valgum. Radiological examination showed platyspondyly, irregular metaphyseal radiolucencies intermingled with radiodensities, and corner fractures. The patient has a c.3275G > A; p.Gly1092Asp mutation in exon 47 of the COL2A1 gene and a variant of unknown significance in c.1366–13C > A in intron 21. This latter sequence variant could partially or completely disrupt the natural splice acceptor site of intron 21/exon 22 in the COL2A1 gene leading to a potential modification of the phenotypic severity.

Keywords

skeletal dysplasia - spondylometaphyseal dysplasia Algerian type - COL2A1 gene

Publikationsverlauf

Eingereicht: 10. Februar 2021

Angenommen: 07. Juni 2021

Artikel online veröffentlicht:
26. Juli 2021

• References

• 1 Kozlowski K, Bacha L, Massen R, Ayati M, Sator S, Brahimi L. A new type of spondylo-metaphyseal dysplasia--Algerian type. Report of five cases. Pediatr Radiol 1988; 18 (03) 221-226
• 2 Rybak M, Foley TP, Kozlowski K. Spondylo-metaphyseal dysplasia Algerian type: confirmation of a new syndrome. Am J Med Genet 1991; 40 (03) 304-306
• 3 Schmidt BJ, Becak W, Becak ML. et al. Metaphyseal dysostosis. Review of literature; study of a case with cytogenetic analysis. J Pediatr 1963; 63: 106-112
• 4 Matsubayashi S, Ikema M, Ninomiya Y, Yamaguchi K, Ikegawa S, Nishimura G. COL2A1 mutation in spondylometaphyseal dysplasia Algerian type. Mol Syndromol 2013; 4 (03) 148-151
• 5 Barat-Houari M, Sarrabay G, Gatinois V. et al. Mutation update for COL2A1 gene variants associated with type II collagenopathies. Hum Mutat 2016; 37 (01) 7-15
• 6 Sambrook J, Fritsch EF, Maniatis T. Molecular Cloning: A Laboratory Manual. 2nd ed.. New York, NY: Cold Spring Harbor Laboratory Press; 1989
• 7 Mortier GR, Cohn DH, Cormier-Daire V. et al. Nosology and classification of genetic skeletal dysplasias. Am J Med Genet 2019; 179: 2393-2419
• 8 Spranger JW, Brill PW, Hall C, Nishimura G, Superti-Furga A, Unger S. Bone Dysplasias: An Atlas of Genetic Disorders of Skeletal Development. 4th ed.. Oxford, United Kingdom: Oxford University Press; 2018
• 9 Adzhubei IA, Schmidt S, Peshkin L. et al. A method and server for predicting damaging missense mutations. Nat Methods 2010; 7 (04) 248-249
• 10 Choi Y, Chan AP. PROVEAN web server: a tool to predict the functional effect of amino acid substitutions and indels. Bioinformatics 2015; 31 (16) 2745-2747
• 11 Schwarz JM, Cooper DN, Schuelke M, Seelow D. MutationTaster2: mutation prediction for the deep-sequencing age. Nat Methods 2014; 11 (04) 361-362
• 12 Auton A, Brooks LD, Durbin RM. et al; 1000 Genomes Project Consortium. A global reference for human genetic variation. Nature 2015; 526 (7571): 68-74
• 13 Desmet FO, Hamroun D, Lalande M, Collod-Béroud G, Claustres M, Béroud C. Human Splicing Finder: an online bioinformatics tool to predict splicing signals. Nucleic Acids Res 2009; 37 (09) e67
• 14 Zhang B, Zhang Y, Wu N, Li J, Liu H, Wang J. Integrated analysis of COL2A1 variant data and classification of type II collagenopathies. Clin Genet 2020; 97 (03) 383-395
• 15 Deng H, Huang X, Yuan L. Molecular genetics of the COL2A1-related disorders. Mutat Res Rev Mutat Res 2016; 768: 1-13
• 16 Kawano O, Nakamura A, Morikawa S, Uetake K, Ishizu K, Tajima T. Spondyloepiphyseal dysplasia congenita caused by double heterozygous mutations in COL2A1. Am J Med Genet A 2015; 167 (07) 1578-1581