A novel homozygous variant in CANT1 causes Desbuquois dysplasia type 1 in a Chinese family and review of literatures

Abstract

Desbuquois dysplasia (DBQD) is a severe chondrodysplasia characterized by short stature, retarded development, multiple joint dislocations, and a distinct radiological appearance of the proximal femur. Pathogenic variants in the calcium-activated nucleotidase 1 (CANT1) or xylosyltransferase 1 (XYLT1) gene have been previously reported to cause DBQD. Here we present a 12-year-old boy manifesting the typical features of DBQD type 1 caused by a homozygous intronic variant c.836-9G>A of CANT1. To our knowledge, this is the first DBQD case described in China revealing that a CANT1 variant was also responsible for DBQD in the Chinese population and further emphasizing the role of CANT1 variants in the etiology of DBQD type 1. Our finding provides certainty for the DBQD clinical diagnosis of this patient and expands the spectrum of known DBQD genetic risk factors. On the basis of this study, amniocentesis-based prenatal diagnosis or preimplantation genetic diagnosis (PGD)-based assisted reproduction could be a helpful aristogenesis strategy to avoid the birth of a DBQD affected child.

Keywords: CANT1 variant; Desbuquois dysplasia; aristogenesis; clinical diagnosis.

Figure 1

Clinical photographs and CANT1 variant identification. (A-C) The appearance of the patient aged 12. Short stature, special facial traits, and abnormal hands are shown. (D) Radiographs of the patient’s pelvis, the typical “Swedish key” appearance of the proximal femur is shown. (E and F). Radiographs of the patient’s knees. Lateral view of the left (E) and right knees (F) exhibit dislocated patella and joints dislocation. (G and H) represent lateral and front views of the patient’s thoracic vertebra. Thoracic abnormality (G) and scoliosis (H) are found. (I and J) Pedigree and Sanger validation of c.836-9G>A in the consanguineous family. Squares indicate male family members, circles indicate female members, a black solid circle and an arrow indicate the patient. (K) Schematic diagram of the CANT1 transcript NM_138793. The blue and blank areas represent the coding region and UTR of the exons, respectively. The arrows indicate the position of the variant. Capital and lowercase letters represent the exon and intron sequence, respectively. The underlines in bold indicate splice sites.