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Abstract：
BACKGROUND: ALG3-CDG is a rare autosomal recessive disease. It is characterized by deficiency of alpha-1,3-mannosyltransferase caused by pathogenic variants in the ALG3 gene. Patients manifest with severe neurologic, cardiac, musculoskeletal and ophthalmic phenotype in combination with dysmorphic features, and almost half of them die before or during the neonatal period.
METHODS: A 23 months-old girl presented with severe developmental delay, epilepsy, cortical atrophy, cerebellar vermis hypoplasia and ocular impairment. Facial dysmorphism, clubfeet and multiple joint contractures were observed already at birth. Transferrin isoelectric focusing revealed a type 1 pattern. Funduscopy showed hypopigmentation and optic disc pallor. Profound retinal ganglion cell loss and inner retinal layer thinning was documented on spectral-domain optical coherence tomography imaging. The presence of optic nerve hypoplasia was also supported by magnetic resonance imaging. A gene panel based next-generation sequencing and subsequent Sanger sequencing identified compound heterozygosity for two novel variants c.116del p.(Pro39Argfs*40) and c.1060 C > T p.(Arg354Cys) in ALG3.
CONCLUSIONS: Our study expands the spectrum of pathogenic variants identified in ALG3. Thirty-three variants in 43 subjects with ALG3-CDG have been reported. Literature review shows that visual impairment in ALG3-CDG is most commonly linked to optic nerve hypoplasia.
METHODS: A 23 months-old girl presented with severe developmental delay, epilepsy, cortical atrophy, cerebellar vermis hypoplasia and ocular impairment. Facial dysmorphism, clubfeet and multiple joint contractures were observed already at birth. Transferrin isoelectric focusing revealed a type 1 pattern. Funduscopy showed hypopigmentation and optic disc pallor. Profound retinal ganglion cell loss and inner retinal layer thinning was documented on spectral-domain optical coherence tomography imaging. The presence of optic nerve hypoplasia was also supported by magnetic resonance imaging. A gene panel based next-generation sequencing and subsequent Sanger sequencing identified compound heterozygosity for two novel variants c.116del p.(Pro39Argfs*40) and c.1060 C > T p.(Arg354Cys) in ALG3.
CONCLUSIONS: Our study expands the spectrum of pathogenic variants identified in ALG3. Thirty-three variants in 43 subjects with ALG3-CDG have been reported. Literature review shows that visual impairment in ALG3-CDG is most commonly linked to optic nerve hypoplasia.
摘要：
背景：ALG3-CDG是一种罕见的常染色体隐性遗传病。其特征在于由ALG3基因中的致病变体引起的α-1,3-甘露糖基转移酶的缺乏。患者表现为严重的神经系统，心脏,肌肉骨骼和眼科表型与畸形特征相结合，其中几乎一半在新生儿期之前或期间死亡。
方法：一名23个月大的女孩出现严重的发育迟缓，癫痫,皮质萎缩,小脑疣发育不全和眼损害。面部畸形,出生时已经观察到马蹄内翻足和多个关节挛缩。转铁蛋白等电聚焦显示1型模式。Funduscopy显示色素减退和视盘苍白。在光谱域光学相干断层扫描成像中记录了深视网膜神经节细胞丢失和内部视网膜层变薄。磁共振成像也支持视神经发育不全的存在。基于下一代测序和随后的Sanger测序的基因组鉴定了ALG3中两个新变体c.116delp.(Pro39Argfs*40)和c.1060C>Tp.(Arg354Cys)的化合物杂合性。
结论：我们的研究扩大了在ALG3中鉴定的致病变异的范围。已经报道了43名患有ALG3-CDG的受试者中的33种变体。文献综述显示，ALG3-CDG的视觉障碍最常见的是与视神经发育不全有关。
方法：一名23个月大的女孩出现严重的发育迟缓，癫痫,皮质萎缩,小脑疣发育不全和眼损害。面部畸形,出生时已经观察到马蹄内翻足和多个关节挛缩。转铁蛋白等电聚焦显示1型模式。Funduscopy显示色素减退和视盘苍白。在光谱域光学相干断层扫描成像中记录了深视网膜神经节细胞丢失和内部视网膜层变薄。磁共振成像也支持视神经发育不全的存在。基于下一代测序和随后的Sanger测序的基因组鉴定了ALG3中两个新变体c.116delp.(Pro39Argfs*40)和c.1060C>Tp.(Arg354Cys)的化合物杂合性。
结论：我们的研究扩大了在ALG3中鉴定的致病变异的范围。已经报道了43名患有ALG3-CDG的受试者中的33种变体。文献综述显示，ALG3-CDG的视觉障碍最常见的是与视神经发育不全有关。
