# First Thai Case of Lethal Desbuquois Dysplasia Type I Caused by Novel Compound Heterozygous CANT1 Mutations: Expanding the Molecular Spectrum

## TL;DR

This paper reports the first Thai case of a rare lethal bone disorder caused by new mutations in the CANT1 gene, expanding our understanding of the condition in Southeast Asia.

## Contribution

The study identifies novel compound heterozygous CANT1 mutations in a Thai patient, expanding the molecular spectrum of DBQD1.

## Key findings

- Compound heterozygous CANT1 missense variants c.505G > A and c.1028G > T were identified in a Thai patient with DBQD1.
- 3D structural modeling suggests the mutations affect calcium binding and protein folding, impairing enzymatic function.
- The case highlights the importance of genetic counseling and prenatal diagnosis for DBQD1 in Southeast Asian populations.

## Abstract

Desbuquois dysplasia Type 1 (DBQD1) is an extremely rare autosomal recessive skeletal dysplasia characterized by severe short stature, joint laxity, distinct facial dysmorphism, and advanced carpotarsal ossification. Here, we report the first Thai patient diagnosed with classical lethal DBQD1. A 38‐week male infant presented with multiple dysmorphic features, micromelia, joint dislocations, narrow thorax, and respiratory insufficiency leading to death at seven months of age. Radiographic findings revealed hallmark features, including a “Swedish key” appearance of the proximal femur and characteristic hand and foot anomalies. Whole exome sequencing identified compound heterozygous missense variants of c.505G > A (p.Asp169Asn) and c.1028G > T (p.Gly343Val) in the CANT1 gene. The 3D structural modeling revealed that both variants reside in conserved regions, with predicted effects on calcium binding and protein folding, resulting in impaired enzymatic function and proteoglycan synthesis. Genetic counseling was provided to the family, and prenatal or preimplantation genetic diagnosis was discussed as an option for future pregnancies. Our report expands the mutational spectrum of the CANT1 gene, contributing to a better understanding of DBQD1’s clinical and molecular presentation, particularly in Southeast Asian populations.