A novel small deletion in CWC27 gene associated with CWC27-related spliceosomeopathy

ABSTRACT

Background

CWC27-related spliceosomeopathy is a rare autosomal recessive disorder with only 14 patients have been reported. It is characterized by retinal degeneration, short stature, skeletal anomalies, and neurological defects. We described the clinical features of a Chinese patient with CWC27-related spliceosomeopathy and identified the pathogenic variant.

Methods

The affected subject underwent detailed ophthalmic examinations. Systemic abnormalities were assessed, including body height, craniofacial morphology, oral cavity, hands, feet, hair and skin. Genomic DNA was isolated from peripheral blood and sequenced by next-generation sequencing. Sanger sequencing was performed for validation and segregation.

Results

The patient had poor vision, nyctalopia and nystagmus from childhood. Fundoscopy revealed extensive chorioretinal atrophy with numerous scattered greyish pigmentation. Severe circular areas of macular atrophy were observed. Optical coherent tomography showed reduced retinal thickness with nearly absent ellipsoid zone and retinal pigment epithelium. In addition, craniofacial abnormalities, short statue, brachydactyly, dental anomalies, cafe-au-lait spots, scant hair, absent eyebrows and thin eyelashes were documented. Genetic analysis revealed a novel homozygous novel small deletion c.1133delG(p.G378Efs*12) in CWC27 (NM_005869.2).

Conclusions

We present a patient with early-onset retinitis pigmentosa and marked syndromic features. A novel CWC27 pathogenic variant was identified. Our findings broaden the clinical and mutation spectrum of CWC27-related spliceosomeopathy, and could be helpful in diagnosis of this rare disease.

KEYWORDS:

• CWC27-related spliceosomeopathy
• CWC27 gene
• syndromic retinitis pigmentosa

Acknowledgments

We would like to thank the patients who participated in the study.

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/13816810.2024.2368791.

Additional information

Funding

This work was supported by Young and Middle-aged Key Personnel Training Project of Fujian Provincial Health Commission [2021GGB008].