Novel WTX nonsense mutation in a family diagnosed with osteopathia striata with cranial sclerosis Case report

Rationale: Osteopathia striata with cranial sclerosis is characterized by linear striations in the metaphysis of the long bones and pelvis with cranial sclerosis. It is an X-linked dominant sclerosing bone dysplasia and affected males show fetal or neonatal lethality. Mutations in the gene encoding Wilms tumor on the X chromosome (WTX) was identified as the cause of X-linked osteopathia striata with cranial sclerosis. About 30 pathogenic mutations in WTX have been reported recently. We have identified a novel nonsense mutation in the family diagnosed as osteopathia striata with cranial sclerosis. Patient concerns: The proband came to our attention at age 9 for the evaluation of toe-out gait and planovalgus deformity. Clinically, the proband showed coarse facial features including frontal bossing, ocular hypertelorism, wide depressed nasal bridge, dental malocclusion, mild macrocephaly and low set ears. Radiologically, sclerotic linear striations were seen in the X-rays of the pelvis and the metaphyseal region of femur and tibia and the cranial sclerosis was observed. The proband's mother presented similar facial features and the X-rays of the pelvis, femur, and tibia revealed same sclerotic linear striations as the proband's. Diagnoses: Osteopathia striata with cranial sclerosis. Interventions: A genetic analysis was conducted on genomic DNA isolated from peripheral blood leukocytes of the proband and the mother for confirming the clinical suspicion of osteopathia striata with cranial sclerosis. WTX on Xq11.2 gene was analyzed in direct sequencing for coding exons including intron-exon boundaries. Outcomes: One novel nonsense mutation (c.1003C>T, p.Gln335*) and known single nucleotide variant were observed in a heterozygous form. Lessons: We found a novel nonsense mutation in a family diagnosed as osteopathia striata with cranial sclerosis. The relationship between various clinical features and genetic mutations can be clarified by accumulation of genetic database.