Department of Biological and Medical Sciences, Faculty of Health and Life Sciences, Oxford Brookes University, Oxford, UK.
Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy.
Eur J Hum Genet. 2023 Oct;31(10):1175-1180. doi: 10.1038/s41431-023-01342-8. Epub 2023 Mar 31.
Biallelic pathogenic variants in ALDH1A3 are responsible for approximately 11% of recessively inherited cases of severe developmental eye anomalies. Some individuals can display variable neurodevelopmental features, but the relationship to the ALDH1A3 variants remains unclear. Here, we describe seven unrelated families with biallelic pathogenic ALDH1A3 variants: four compound heterozygous and three homozygous. All affected individuals had bilateral anophthalmia/microphthalmia (A/M), three with additional intellectual or developmental delay, one with autism and seizures and three with facial dysmorphic features. This study confirms that individuals with biallelic pathogenic ALDH1A3 variants consistently manifest A/M, but additionally display neurodevelopmental features with significant intra- and interfamilial variability. Furthermore, we describe the first case with cataract and highlight the importance of screening ALDH1A3 variants in nonconsanguineous families with A/M.
双等位基因致病性 ALDH1A3 变异导致约 11%的隐性遗传严重眼部发育异常病例。一些个体可能表现出可变的神经发育特征，但与 ALDH1A3 变异的关系尚不清楚。在这里，我们描述了七个无关的具有双等位基因致病性 ALDH1A3 变异的家庭：四个复合杂合子和三个纯合子。所有受影响的个体均表现为双侧无眼症/小眼球症（A/M），其中三人伴有智力或发育迟缓，一人伴有自闭症和癫痫发作，三人伴有面部畸形特征。本研究证实，具有双等位基因致病性 ALDH1A3 变异的个体始终表现为 A/M，但另外还表现出具有显著的个体内和家族间变异性的神经发育特征。此外，我们描述了首例伴有白内障的病例，并强调了在非近亲婚配的 A/M 家族中筛查 ALDH1A3 变异的重要性。
