Novel mutations in <i>MFRP</i> and <i>PRSS56</i> are associated with posterior microphthalmos

Abstract

<b>Background</b>: Biallelic pathogenic variants in <i>MFRP</i> and <i>PRSS56</i> genes can be responsible for nanophthalmos (NO) or posterior microphthalmos (PM). This study describes detailed clinical and molecular findings in a series of five patients affected by PM from four unrelated families.<b>Materials and Methods</b>: All patients underwent a complete ophthalmological and genetic evaluation. For proper and deep phenotyping a multimodal instrumental approach was used for all cases: B-scan ultrasound, spectral domain optical coherence tomography (SD-OCT), fundus retinal imaging and anterior segment data were obtained. Molecular analysis of <i>PRSS56</i> and <i>MFRP</i> genes was performed with Next-Generation Sequencing (NGS) methodology and segregation analysis on parents and one affected sibling was performed with Sanger sequencing.<b>Results</b>: A very high hyperopia of +14.00D or more was the main refractive error and macular abnormalities were identified in all patients. Axial length ranged from 15.3 mm to 17.86 mm (mean 16.58 mm) and age at first presentation ranged from 6 to 36 months (mean 18 months). Anterior chamber depth was within normal values, according to age, while total axial length was severely reduced in all patients. All our patients met the diagnostic criteria for PM. Three patients, including a pair of siblings, carried compound heterozygous mutations in the <i>PRSS56</i> gene; in the other two patients, one homozygous or two compound heterozygous mutations in the <i>MFRP</i> gene were detected.<b>Conclusion</b>: Our study describes four novel mutations in the <i>PRSS56</i> gene and one in the <i>MFRP</i> gene in patients with non-syndromic posterior microphthalmos. Proper genotype-phenotype correlation and early diagnosis could lead to good functional results.