Molecular analysis of patients with aniridia in Russian Federation broadens the spectrum of PAX6 mutations.
Congenital aniridia is a severe autosomal dominant congenital panocular disorder, mainly associated with pathogenic variants in the PAX6 gene. The objective of the study was to investigate the mutational and clinical spectra of congenital aniridia in a cohort of 117 patients from Russia. Each patient underwent detailed ophthalmological examination. From 91 unrelated families, 110 patients were diagnosed with congenital aniridia and 7 with WAGR syndrome (Wilms tumor, Aniridia, Genitourinary anomalies, and mental Retardation syndrome). The clinical presentation in aniridia patients varied from the complete bilateral absence of the iris (75.5%) to partial aniridia or iris hypoplasia (24.5%). Additional ocular abnormalities were consistent with previous reports. In our cohort, we saw a previously not described high percentage of patients (45%) who showed non-ocular phenotypes. Prevalence of deletions coherent with WAGR syndrome appeared to be 19.4% out of sporadic patients. Among the other aniridia cases, PAX6 deletions were identified in 18 probands, and small intragenic changes were detected in 58 probands with 27 of these mutations being novel and 21 previously reported. In 3 families mosaic mutation was transmitted from a subtly affected parent. Therefore, PAX6 mutations explained 96.7% of aniridia phenotypes in this study with only 3 of 91 probands lacking pathogenic variants in the gene.
Federal State Budgetary Institution 'Research Center for Medical Genetics', Moscow, Russian Federation.
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TA
Vasilyeva
Department of Ambulant Surgery and Conservative Treatment, Cheboksary Branch of S. Fyodorov Eye Microsurgery Federal State Institution, Cheboksary, Russian Federation.
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AA
Voskresenskaya
German Aniridia Center at the Section of Pediatric Ophthalmology, Orthoptics, Low Vision & Neuroophthalmology, Department of Ophthalmology, Saarland University Homburg/Saar, Germany.
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B
Käsmann-Kellner
Federal State Budgetary Institution 'Research Center for Medical Genetics', Moscow, Russian Federation.
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OV
Khlebnikova
Department of Ambulant Surgery and Conservative Treatment, Cheboksary Branch of S. Fyodorov Eye Microsurgery Federal State Institution, Cheboksary, Russian Federation.
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NA
Pozdeyeva
Federal State Budgetary Institution 'Research Center for Medical Genetics', Moscow, Russian Federation.
G M
GM
Bayazutdinova
Federal State Budgetary Institution 'Research Center for Medical Genetics', Moscow, Russian Federation.|Department of Molecular and Cell Genetics, Pirogov Russian National Research Medical University, Moscow, Russian Federation.
S I
SI
Kutsev
Federal State Budgetary Institution 'Research Center for Medical Genetics', Moscow, Russian Federation.
E K
EK
Ginter
Division of Developmental Biology, Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin.
E V
EV
Semina
Federal State Budgetary Institution 'Research Center for Medical Genetics', Moscow, Russian Federation.|Laboratory of Functional Analysis of the Genome, Moscow Institute of Physics and Technology (State University), Dolgoprudny, Moscow Region, Russian Federation.
A V
http://orcid.org/0000-0002-0972-5118
AV
Marakhonov
Federal State Budgetary Institution 'Research Center for Medical Genetics', Moscow, Russian Federation.|Department of Molecular and Cell Genetics, Pirogov Russian National Research Medical University, Moscow, Russian Federation.
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RA
Zinchenko
D000328:Adult; D000483:Alleles; D015783:Aniridia / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D015331:Cohort Studies; D005091:Exons; D005260:Female; D015870:Gene Expression; D020022:Genetic Predisposition to Disease; D006801:Humans; D007223:Infant; D040582:Inheritance Patterns; D007438:Introns; D008297:Male; D009154:Mutation; D000071841:PAX6 Transcription Factor / Q000235:genetics*; D010641:Phenotype; D012426:Russia; D012720:Severity of Illness Index; D017624:WAGR Syndrome / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology
D000071841:PAX6 Transcription Factor; C000605730:PAX6 protein, human

CNS involvement; 
OMIM #106210; 
PAX6 syndrome; de novo mutations; iris hypoplasia; large deletions; non-ocular complications; novel mutations