Dataset Information

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.

SUBMITTER: Kuang L

PROVIDER: S-EPMC7476945 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Kuang Lele L Liu Bin B Peng Rui R Xi Di D Gao Yuping Y

International journal of clinical and experimental pathology 20200801 8

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 o ...[more]

PMID: 32922611

Similar Datasets

Project description:BACKGROUND:Spondyloepiphyseal dysplasia tarda (SEDT) is a rare X-linked recessive inherited osteochondrodysplasia caused by mutations in the TRAPPC2 gene. It is clinically characterized by disproportionate short stature and early onset of degenerative osteoarthritis. Clinical diagnosis can be challenging due to the late-onset of the disease and lack of systemic metabolic abnomalites. Genetic diagnosis is critical in both early diagnosis and management of the disease. Here we reported a five-generation Chinese SEDT family and described the novel molecular findings. METHODS:Detailed family history and clinical data were collected. Genomic DNA was extracted from venous blood samples of family members. The exons of genes known to be associated with skeletal disorders were captured and deep sequenced. Variants were annotated by ANNOVAR and associated with multiple databases. Putative variants were confirmed by Sanger sequencing. The identified variant was classified according to the American College of Medical Genetics (ACMG) criteria. RESULTS:The proband was a 27-year-old Chinese male who presented with short-trunk short stature and joint pain. His radiographs showed platyspondyly with posterior humping, narrow hip-joint surfaces, and pelvic osteosclerosis. A pedigree analysis of 5 generations with 6 affected males revealed an X-linked recessive mode of inheritance. Affected males were diagnosed as SEDT according to the clinical and radiological features. Next-generation sequencing identified a novel variant of c.216_217del in the exon 4 of TRAPPC2 gene in the proband and other affected males. This variant resulted in the shift of reading frame and early termination of protein translation (p.S73Gfs*15). The mother and maternal female relatives of the proband were heterozygous carriers of the same variant, while no variations were detected in this gene of his father and other unaffected males. Based on the ACMG criteria, the novel c.216_217del variant of the TRAPPC2 gene was the pathogenic variant of this SEDT family. CONCLUSION:In this study we identified the novel pathogenic variant of of c.216_217del in the gene of TRAPPC2 in this five-generation Chinese SEDT family. Our findings expand the clinical and molecular spectrum of SEDT and helps the genetic diagnosis of SEDT patients.

Dataset Information

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

Publications

A novel homozygous variant in <i>CANT1</i> causes Desbuquois dysplasia type 1 in a Chinese family and review of literatures.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets