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

Francisco Cammarata-Scalisi; Uta Matysiak; Colin E. Willoughby; Gunda Ruzaike; Antonio Cárdenas Tadich; Maykol Araya Castillo; Carmen Zara-Chirinos; Ana Bracho; Andrea Avendaño; Houweyda Jilani; Michele Callea

doi:10.1055/s-0041-1732474

Journal of Pediatric Genetics, Table of Contents

J Pediatr Genet 2023; 12(04): 339-341
DOI: 10.1055/s-0041-1732474

Case-Based Review

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

Francisco Cammarata-Scalisi

¹Departamento of Pediatrics, Regional Hospital of Antofagasta, Antofagasta, Chile

,

Uta Matysiak

²Department of Pediatrics, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

,

Colin E. Willoughby

³Genomic Medicine, School of Biomedical Sciences, Ulster University, Northern Ireland, United Kingdom

,

Gunda Ruzaike

²Department of Pediatrics, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

,

Antonio Cárdenas Tadich

¹Departamento of Pediatrics, Regional Hospital of Antofagasta, Antofagasta, Chile

,

Maykol Araya Castillo

⁴Clinical Laboratory, Regional Hospital of Antofagasta, Chile

,

Carmen Zara-Chirinos

⁵Institute of Genetic Research, Faculty of Medicine, University of Zulia, Maracaibo, Venezuela

,

Ana Bracho

⁵Institute of Genetic Research, Faculty of Medicine, University of Zulia, Maracaibo, Venezuela

,

Andrea Avendaño

⁶Division of Medical Genetics, Department of Pediatrics, Faculty of Medicine, University of Los Andes, Mérida, Venezuela

,

Houweyda Jilani

⁷Genetic Department, Mongi Slim Hospital, Marsa, Tunisia

⁸Faculty of Medicine of Tunis, University of Tunis El Manar, Tunisia

,

Michele Callea

⁹Meyer Children's Hospital, IRCCS, Florence, Italy

› Author Affiliations

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

Full Text

References

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