目的:食物不良反应,经常被低估,包括先天性单糖-二糖代谢紊乱,产生不同的结果,如腹痛,腹泻,出血性疾病,甚至死亡。这项研究回顾了与这些疾病相关的遗传变异,在接受全外显子组序列分析(WES)的队列中,确定载波频率和基因型-表型相关性。
方法:来自484名患者的数据,使用基因面板(ALDOB,FBP1,GALE,GALK1,GALM,GALT,LCT,SLC2A2,SLC5A1,SI)用于先天性单糖-二糖代谢障碍。使用xGenExome研究小组v2试剂盒对患者进行WES,利用下一代序列分析(NGS)。这项研究包括致病性,可能致病,和不确定显著性变体(VUS)变体。
结果:在484名患者中(244名女性,240男性),在所分析的基因中,17.35%携带99个变体(67个不同的)。致病/可能致病等位基因频率为0.013,而VUS等位基因频率为0.088。值得注意的是,44%(37/84)的突变患者表现出至少一种相关表型。运输频率范围从1:25(SI基因)到1:968(GALE基因),估计疾病频率从1:2500到1:3748000。
结论:我们的研究强调了隐性遗传病杂合携带者的临床表现,解决先天性单糖-二糖代谢紊乱的携带者频率和表型效应的差距。这些知识可以改善这些疾病的诊断和管理,可能预防不良食物反应及其相关并发症。
OBJECTIVE: Adverse food reactions, often underestimated, encompass congenital monosaccharide-disaccharide metabolism disorders, yielding diverse outcomes such as abdominal pain, diarrhea, bleeding disorders, and even death. This study retrospectively scrutinized genetic variants linked to these disorders in a cohort subjected to whole-exome sequence analysis (WES), determining carrier frequencies and genotype-phenotype correlations.
METHODS: Data from 484 patients, were retrospectively analyzed using a gene panel (ALDOB, FBP1, GALE, GALK1, GALM, GALT, LCT, SLC2A2, SLC5A1, SI) for congenital monosaccharide-disaccharide metabolism disorders. WES was performed on patients using the xGen Exome Research Panel v2 kit, utilizing Next Generation Sequence Analysis (NGS). The study encompassed pathogenic, likely pathogenic, and variant of uncertain significance (VUS) variants.
RESULTS: Among 484 patients (244 female, 240 male), 17.35% carried 99 variants (67 distinct) in the analyzed genes. Pathogenic/likely pathogenic allele frequency stood at 0.013, while VUS allele frequency was 0.088. Notably, 44% (37/84) of patients harboring mutations manifested at least one relevant phenotype. Carriage frequencies ranged from 1:25 (SI gene) to 1:968 (GALE gene), with the estimated disease frequency spanning from 1:2500 to 1:3748000.
CONCLUSIONS: Our study underscores clinical manifestations in heterozygous carriers of recessive genetic disorders, addressing gaps in carrier frequencies and phenotypic effects for congenital monosaccharide-disaccharide metabolism disorders. This knowledge can improve these conditions\' diagnosis and management, potentially preventing adverse food reactions and their associated complications.