APHP-Centre, Service de Néphrologie Pédiatrique, Centre de Référence des Maladies Rénales Héréditaires de l'Enfant et de l'Adulte (MARHEA), Hôpital Universitaire Necker-Enfants malades, Institut Imagine, Université Paris-Cité, Paris, France.
Service de Néphrologie Pédiatrique, Centre Hospitalier Universitaire Felix Guyon, Saint Denis, France.
Clin Genet. 2023 Jan;103(1):114-118. doi: 10.1111/cge.14229. Epub 2022 Sep 17.
Integrin Subunit Alpha 8 gene (ITGA8) encodes an integrin chain that is known to be critical in the early stage of the kidney development. Bi-allelic pathogenic variants in ITGA8 are associated with bilateral renal agenesis, as well as anomalies involving urogenital system. Here, we report two unrelated patients presenting with slowly progressing chronic kidney disease associated with bilateral renal hypodysplasia carrying homozygous loss of function variants in the ITGA8 gene. These results broaden the clinical and genotypic spectrum of ITGA8 defects, revealing the high and unexpected degree of phenotypic heterogeneity of this autosomal recessive disease. Our study emphasizes the usefulness of Next-Generation Sequencing in unraveling the genetic cause of chronic kidney disease of unknown etiology, and raises the question of genetic modifiers involved in the variation of the phenotypes associated with autosomal recessive ITGA8 pathogenic variants.
整合素亚单位 alpha8 基因（ITGA8）编码一种整合素链，已知在肾脏发育的早期阶段至关重要。ITGA8 的双等位致病性变异与双侧肾发育不全以及涉及泌尿生殖系统的异常有关。在这里，我们报告了两例无关联的患者，他们表现为进展缓慢的慢性肾脏病，伴有双侧肾脏发育不良，携带 ITGA8 基因的纯合功能丧失变异。这些结果拓宽了 ITGA8 缺陷的临床和基因型谱，揭示了这种常染色体隐性疾病高度和意外的表型异质性。我们的研究强调了下一代测序在揭示不明病因的慢性肾脏病的遗传原因方面的有用性，并提出了与常染色体隐性 ITGA8 致病性变异相关的表型变化涉及遗传修饰因子的问题。
