Introduction: The X-linked recessive chondrodysplasia punctata (CDPX1) is a rare skeletal dysplasia caused by mutation in the arylsulfatase E (ARSE) gene located at Xp22.3. It was first described by Curry et al, affects about less than 1 in 500,000 individuals, and is characterized by punctate calcification in the endochondral bone leading to stippled epiphysis, severe nasal and midfacial hypoplasia, and distal phalangeal hypoplasia (brachytelephalangy). Here we describe a baby boy with a hemizygous missense mutation in the ARSE gene and his mother and sister with heterozygous mutation unremarkable clinical history, which has not been reported earlier. Case: A male infant was admitted because of dysmorphic features of face and limbs. His mother was 37 years old, and his father was 40 years old. His mother’s obstetric history was gravida 3, para 2, and first baby unknown sex who was detected macrocephaly, depressed nasal bone and shortened limbs on antenatal ultrasonography was died as soon as birth at about 25 weeks gestation. He was born at the 37+3 week of gestation, weight was 3,250 g (50~75th centile), height 48 cm (50~75th centile), head circumference 36.5 cm (above 90th centile). He had depressed nasal bridge and brachytelephalangia. Radiographs showed incomplete ossification of whole vertebrae, and diffuse epiphyseal punctate calcifications of vertebrae, humerus, femurs, and proximal tarsal bones, and brachytelephalangia of both hands. Spine MRI showed atlantoaxial dislocations and compressive myelopathy at C1/C2 level. He got a foramen magnum decompression and C1 laminectomy operation and discharged without symptoms of spinal cord compression. Direct sequencing analyses revealed a hemizygous missense mutation in the ARSE gene (c.430G＞A; p.Gly144Arg), which mutation has not been reported previously. The mother and older sister were both heterozygous for the same mutation as in the proband. The proband’s father was shown to be hemizygous for the wild-type G allele. Conclusion: We report a case of CDPX1 with novel missense mutation in the ARSE gene, replacing glycine with arginine at codon 144 (c.430G＞A; p.Gly144Arg), accompanying severe spinal cord compression successfully corrected by cervical decompression operation.