한국인 선천성 무홍채증의 임상양상과 분자유전학적 특성
Clinical Features and Molecular Characteristics of Korean Patients with Congenital Aniridia
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목적: 한국인 선천성 무홍채증 환자의 임상양상과 분자유전학적 특성을 분석하여 소개한다. 대상과 방법: 홍채형성저하증을 특징으로 임상적으로 진단된 한국인 선천성 무홍채증 환자를 대상으로 하였다. 최대교정시력, 홍채형성저하증의 정도, 황반형성저하증의 정도 및 동반된 이상소견을 기록하여 분석하였다. PAX6 유전자의 변이분석, 복합결찰의존프로브증폭법 분석, 유전체의 분자 핵형 분석 및 후보 유전자 염기서열 분석을 통한 분자유전학적 검사결과를 분석하였다. 결과: 18가계의 총 28명의 환자가 포함되었다. 최대교정시력은 다양하여 시표로 측정이 가능하였던 19명에서 20/400에서 20/25의 범위였고, 그중 20/200 이하의 시력을 보인 환자는 9명이었다(47%). 황반형성저하증은 전 예에서 관찰되었고, 그중 1명은 매우 경증이었다. PAX6 유전자 분석을 시행한 18가계 중 13가계에서 유전자 변이가 발견되었으며, 2개의 새로운 변이(p.Trp162Leufs*38, p.Gly409Arg)가 발견되었다. 발견된 변이 중 3가계에서는 과오돌연변이(missense mutation), 또 다른 3가계에서는 PAX6 유전자 부위의 큰 결손(large chromosomal deletions)을 보였다. 결론: 선천성 무홍채증과 연관된 2개의 새로운 변이를 발견하여 보고하는 바이다. 선천성 무홍채증은 시력을 위협하는 심각한 안구기형이지만, 중심시력, 홍채형성저하증의 정도는 매우 다양하였다. 전체 가계의 72%에서 PAX6 유전자의 돌연변이가 발견되었고, 돌연변이 유무에 관계없이 경증에서 중증까지 다양한 스펙트럼의 임상양상을 보여주었다.
Abstract
Purpose: To introduce clinical features and molecular characteristics of Korean patients with congenital aniridia. Methods: Patients with iris hypoplasia were diagnosed clinically as congenital aniridia and were included in the study. Best corrected visual acuity (BCVA) and associated ocular abnormalities (including severity of iris hypoplasia, nystagmus, keratopathy, and foveal hypoplasia), and findings in optical coherence tomography were analyzed. PAX6 analysis,multiplex ligation-dependent probe amplification (MLPA), genomic molecular karyotyping, and candidate gene sequencing were performed to detect genetic abnormalities. Results: 28 patients from 18 families were included in the study. BCVA varied from hand motion to 20/25. No manifest nystagmus was found in 3 patients, but the rest of the patients had pendular horizontal nystagmus. Keratopathy was found in 23 patients, cataracts in 12 patients, and glaucoma in 4 patients. All patients had foveal hypoplasia, including one case with a subtle phenotype. The PAX6 mutation was detected in 13 families out of 18;2 (p.Trp162Leufs*38,p.Gly409Arg) were novel,3 families had the miss ensemutation, and 3 families had alargedeletion in the PAX6 gene. Conclusions: This study adds 2 novel PAX6 mutations related to congenital aniridia to those previously reported. Congenital aniridia is a serious, sight-threatening ocular malformation, but central vision and the degree of iris hypoplasia were highly variable. The PAX6 mutation was detected in 72% of the patients in this study, and there were no specific clinical features differentiating aniridia with and without PAX6 mutations.
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