Whole Xp deletion in a girl with mental retardation, epilepsy, and biochemical features of OTC deficiency

Background: Females with a total or partial deletion of the short arm of the X chromosome have variable features of Turner syndrome, but mental retardation (MR) rarely occurs. The haploinsufficiency of deleted genes that escape X-inactivation may explain the occurrence of MR and autism. Ornithine transcarbamylase (OTC) deficiency is the most common urea cycle disorder and is inherited in an X-linked semi-dominant trait, and the OTC gene maps to Xp21. Methods: We report on a girl with MR, epilepsy and biochemical changes characteristic of OTC deficiency but no identifiable point mutation in the OTC gene. Standard G-banding cytogenetic analysis, whole genome karyotyping, and X-inactivation studies were performed to determine the genetic etiology of the OTC deficiency in the patient. Results: Cytogenetic analysis and molecular karyotyping using SNP array revealed a deletion of the whole short arm of the X chromosome (Xp22.33-p11.1). Inactivation studies also revealed a completely skewed X-inactivation. Conclusion: Our patient presented with MR, epilepsy, and some evidence of reduced OTC activity, but performed genetic studies gave no explanation for this phenotype. We hope that this case report contributes to the understanding of the underlying genetic factors of the manifestation of X-linked disorders in female patients.