Abstract:

Objective To retrospectively analyze the clinical diagnosis and treatment processes of children with retinitis pigmentosa, with or without skeletal abnormalities syndrome (RPSKA), and to explore the clinical and genetic characteristics of the disease. Methods The clinical characteristics of one case of RPSKA child and the genetic variations between the child and her mother were analyzed. The effect of the mutation on mRNA splicing was verified and the protein stability was detected. The relevant literature was reviewed and summarized. Results The patient is an 8-year-old girl with short stature(-2.28SD), special face(triangular face, left esotropia, low ear position), and severe intellectual disability (Wechsler intelligence scale for children 37 points). She was diagnosed with retinitis pigmentosa at the age of 3. Whole exome sequencing indicated that the patient carried homozygous splice site variation of CWC27 c.397-1G>A. The splicing mutation produced three kinds of abnormal transcripts. The protein stability of all transcripts decreased obviously. Both of them proved that the mutation is pathogenic. Combined with the clinical phenotype of this patient, she was diagnosed with RPSKA. A total of 17 cases of RPSKA have been reported globally, including this case, there are now 18 documented cases. Conclusions RPSKA caused by CWC27 splicing site mutations typically affects multiple systems. It should be vigilant when encountering patients with retinitis pigmentosa, short stature, intellectual disability, and craniofacial malformations. Genetic testing plays a critical role in achieving a definitive diagnosis.

Key words: CWC27 gene variation, retinitis pigmentosa, intellectual disability, short stature, craniofacial deformity, child