Leveraging genetic testing for cataract diagnosis: novel NHS variant guides the diagnosis to Nance-Horan syndrome, a case study.

BACKGROUND

Nance-Horan Syndrome (NHS) is a rare genetic disorder caused by pathogenic variants in the NHS gene. Phenotypically, NHS is characterized by severe congenital cataracts, dental anomalies, distinct facial features, and developmental defects. Here, we document a novel variant in the NHS gene and investigate the consequent phenotypic manifestations.

METHODS

Ophthalmologic findings along with medical history were gathered through clinical examination and chart review, slit-lamp biomicroscopy, optical coherence tomography, and physical exam alongside genetic testing. Genetic testing through Next-Generation Sequencing (NGS) was performed to investigate the molecular etiology, with variant confirmation and familial segregation analysis conducted using Sanger sequencing.

RESULTS

We identified a novel hemizygous frameshift variant in the NHS gene (c.1861_1862del; p.Met621Glyfs *5), resulting from a dinucleotide deletion, in a patient with bilateral congenital cataracts. Segregation analysis revealed that this variant was maternally inherited. The underlying genetic etiology and op`hthalmic consequences associated with this variant are detailed in this study.

CONCLUSION

This case presents a novel variant in the NHS gene in a symptomatic hemizygous patient, exhibiting significant cataract findings and contributing to the phenotypic spectrum of NHS. This case underscores the importance of genetic testing for NHS and highlights the need for further research on the genetics of NHS.