Genetic studies in a patient with X-linked retinoschisis coexisting with developmental delay and sensorineural hearing loss

ABSTRACT

Background: In this study, we present a juvenile retinoschisis patient with developmental delay, sensorineural hearing loss, and reduced axial tone. X-linked juvenile retinoschisis (XLRS) is a retinal dystrophy, most often not associated with systemic anomalies and also not showing any locus heterogeneity. Therefore it was of interest to understand the genetic basis of the condition in this patient.

Materials and methods: RS1 gene screening for XLRS was performed by Sanger sequencing. Whole genome SNP 6.0 array analysis was carried out to investigate gross chromosomal aberrations that could result in systemic phenotype. In addition, targeted next generation sequencing (NGS) was employed to determine any possible involvement of X-linked syndromic and non-syndromic mental retardation genes. This NGS panel consisted of 550 genes implicated in several other rare inherited diseases.

Results: RS1 gene screening revealed a pathogenic hemizygous splice site mutation (c.78+1G>T), inherited from the mother. SNP 6.0 array analysis did not indicate any significant chromosomal aberrations that could be disease-associated. Targeted resequencing did not identify any mutations in the X-linked mental retardation genes. However, variations in three other genes (NSD1, LARGE, and POLG) were detected, which were all inherited from the patient’s unaffected father.

Conclusions: Taken together, RS1 mutation was found to segregate with retinoschisis phenotype while none of the other identified variations were co-segregating with the systemic defects. Hereby, we infer that the multisystemic defects harbored by the patient are a rare coexistence of XLRS, developmental delay, sensorineural hearing loss, and reduced axial tone reported for the first time in the literature.

KEYWORDS:

• Coexistence
• developmental delay
• retinoschisis
• sensorineural hearing loss
• whole genome analysis

Supplemental data

Supplemental data for this article can be accessed on the publisher’s website at http://dx.doi.org/10.1080/13816810.2016.1214972.

Acknowledgments

We thank the patient and family members for their participation in the study. We would like to acknowledge Dr. Divya Rao for her valuable inputs and support.

Declaration of interest

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

Funding

This work was a part of the project funded by the Department of Biotechnology, India (RGYI scheme; BT/PR15111/GBD/27/322/2011).

Additional information

Funding

This work was a part of the project funded by the Department of Biotechnology, India (RGYI scheme; BT/PR15111/GBD/27/322/2011).