Congenital aniridia (AN) is a hereditary autosomal dominant developmental disorder of the eye. Heterozygous mutations in the PAX6 gene and chromosomal rearrangements involving the 11p13 locus lie behind the pathogenesis of the AN. The key role of the PAX6 gene in the regulation of embryogenesis and the pleiotropic effect of this transcription factor explain the damage of several tissues of the anterior and posterior segments of the eye, brain structures, and the disturbance of morphogenesis and endocrine function of the pancreas observed in AN. Recently AN has been considered a syndromic pathology by several researchers. The review suggests classification and summarizes information on the clinical characteristics and genetic basis of various forms of AN. The problem of discrimination of clinical-genetic variants of the dysgenesis of the anterior segment of the eye and the differential diagnosis of PAX6-associated AN with WAGR syndrome, anterior dysgenesis, other rare monogenic and chromosomal syndromes is discussed, and the role of molecular diagnostics is emphasized.

Introduction. The use of invasive methods for diagnosing primary diffuse large B-cell lymphoma of the central nervous system (PDLBCL CNS) and primary vitreoretinal lymphoma (PVRL) is often associated with the development of severe neurological deficits and disability of patients. A promising direction in the diagnosis of PDLBCL CNS and PVRL is the use of non-invasive approaches based on molecular genetic methods for the determination of mutations in the MYD88 gene in the cerebrospinal fluid (CSF), vitreous fluid (VF) and free circulating tumor DNA (cfDNA) in blood serum.Aim: to present the potential of non-invasive diagnosis of PDLBCL CNS and PVRL.Main findings. The study included 6 patients (4 — PDLBCL CNS, 2 — PVRL). The average age was 64 (54–75) years. Despite increased cytosis in the CSF in all 4 patients with PDLBCL CNS, the tumor population was determined by flow cytometry in only half of the cases. According to a molecular genetic study, mutations in the MYD88 gene with an allelic load from 2.5% to 15% were detected in the genomic DNA of the CSF of all patients. In 2 patients with PVRL, mutations in the MYD88 gene were detected in VF with an allelic load of 4.2% and 6.6%, which was the only confirmation of the diagnosis. Currently, 5 patients have completed the treatment program and 1 is undergoing therapy. All 5 patients are in complete remission (CR) of the disease with follow-up periods from 1 to 8 months.

This study investigates the distribution of PAX6-associated congenital aniridia (AN) and WAGR syndrome across Russian Federation (RF) districts while characterizing PAX6 gene variants. We contribute novel PAX6 pathogenic variants and 11p13 chromosome region rearrangements to international databases based on a cohort of 379 AN patients (295 families, 295 probands) in Russia. We detail 100 newly characterized families (129 patients) recruited from clinical practice and specialized screening studies. Our methodology involves multiplex ligase-dependent probe amplification (MLPA) analysis of the 11p13 chromosome, PAX6 gene Sanger sequencing, and karyotype analysis. We report novel findings on PAX6 gene variations, including 67 intragenic PAX6 variants and 33 chromosome deletions in the 100 newly characterized families. Our expanded sample of 295 AN families with 379 patients reveals a consistent global PAX6 variant spectrum, including CNVs (copy number variants) of the 11p13 chromosome (31%), complex rearrangements (1.4%), nonsense (25%), frameshift (18%), and splicing variants (15%). No genetic cause of AN is defined in 10 patients. The distribution of patients across the Russian Federation varies, likely due to sample completeness. This study offers the first AN epidemiological data for the RF, providing a comprehensive PAX6 variants spectrum. Based on earlier assessment of AN prevalence in the RF (1:98,943) we have revealed unexamined patients ranging from 55% to 87%, that emphases the need for increased awareness and comprehensive diagnostics in AN patient care in Russia.

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