Background: Biallelic pathogenic variants in MFRP and PRSS56 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.Materials and Methods: 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 PRSS56 and MFRP genes was performed with Next-Generation Sequencing (NGS) methodology and segregation analysis on parents and one affected sibling was performed with Sanger sequencing.Results: 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 PRSS56 gene; in the other two patients, one homozygous or two compound heterozygous mutations in the MFRP gene were detected.Conclusion: Our study describes four novel mutations in the PRSS56 gene and one in the MFRP gene in patients with non-syndromic posterior microphthalmos. Proper genotype-phenotype correlation and early diagnosis could lead to good functional results.

中文翻译：

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MFRP和PRSS56中的新型突变与后眼小眼病相关。

背景：MFRP和PRSS56基因中的双等位基因致病变异可能是造成纳米眼（NO）或后眼小（PM）的原因。这项研究描述了来自四个不相关家庭的5例受PM影响的系列患者的详细临床和分子发现。材料与方法：所有患者均接受了完整的眼科和遗传学评估。为了进行适当和深入的表型分析，在所有情况下都使用了一种多模式仪器方法：B扫描超声，光谱域光学相干断层扫描（SD-OCT），眼底视网膜成像和前节数据。使用下一代测序（NGS）方法对PRSS56和MFRP基因进行分子分析，并对父母进行隔离分析，并使用Sanger测序对一个患病兄弟姐妹进行分析。结果：高度远视+14。所有患者的主要屈光不正是00D或更高，并发现了黄斑异常。轴长范围为15.3 mm至17.86 mm（平均16.58 mm），首次出现时的年龄范围为6至36个月（平均18个月）。根据年龄，前房深度在正常值范围内，而所有患者的总轴向长度均明显减少。我们所有的患者均符合PM的诊断标准。3名患者，包括一对兄弟姐妹，在PRSS56基因中携带了复合杂合突变。结论：我们的研究描述了非综合征性后眼小眼病患者的PRSS56基因中的四个新突变和一个MFRP基因中的一个新突变。