Pathology and Laboratory Medicine Department, King Faisal Specialist Hospital and Research Centre, P.O. Box 3354, Riyadh 11211, Saudi Arabia.
Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud University, Riyadh 11433, Saudi Arabia.
Genes (Basel). 2024 Oct 25;15(11):1374. doi: 10.3390/genes15111374.
Nephronophthisis (NPHP) is an autosomal recessive genetic disorder that can cause early-onset kidney failure. plays an important role in early kidney development and encodes a protein that interacts with other proteins within the primary cilium. mutations are known to cause nephronophthisis 16 (NPHP-16). Little is known regarding fetal ultrasound imaging and the antenatal diagnosis of fetuses with -associated kidney disease. Here, we report the detection of variants in consanguineous families with polycystic kidney antenatally and in the early stages of life.
Three unrelated Saudi Arabian patients (two prenatal patients and one neonate) were investigated. These cases were referred to the hospital due to the presence of echogenic kidneys on antenatal scanning. After clinical and phenotypic evaluation, whole-exome sequencing (WES) was performed on the cord and peripheral blood to identify the molecular genetic causes associated with the echogenic kidney phenotypes.
Two homozygous sequence variants were detected in . The homozygous missense novel variant : c.1159A>C was detected in Families 1 and 2. In the third family, the known homozygous loss-of-function variant : c.907+2T>A was detected.
We identified homozygous variants in three families presenting with antenatal polycystic kidney disease. The findings provide an expanded clinical presentation of and emphasize the utility of WES in the diagnosis of echogenic kidneys in prenatal settings.
肾单位肾痨（NPHP）是一种常染色体隐性遗传疾病，可导致早发性肾衰竭。 NPHP1 基因在早期肾脏发育中发挥重要作用，并编码一种与初级纤毛内其他蛋白相互作用的蛋白。已知 NPHP1 基因突变可导致肾单位肾痨 16 型（NPHP-16）。关于与 NPHP1 相关的肾脏疾病胎儿的胎儿超声成像和产前诊断知之甚少。在这里，我们报告了在具有多囊肾的近亲家庭中产前和生命早期阶段检测到 - 相关肾脏疾病的 NPHP1 变异体。
对 3 名来自沙特阿拉伯的无关患者（2 名产前患者和 1 名新生儿）进行了研究。这些病例因产前扫描存在高回声肾脏而被转诊至医院。在进行临床和表型评估后，对脐带和外周血进行全外显子组测序（WES），以鉴定与高回声肾脏表型相关的分子遗传病因。
在 中检测到 2 个纯合序列变异体。在家族 1 和 2 中检测到纯合错义新变异体：c.1159A>C。在第三个家庭中，检测到已知的纯合无功能变异体：c.907+2T>A。
我们在 3 个表现为产前多囊肾病的家庭中鉴定出纯合 NPHP1 变异体。这些发现提供了 NPHP1 的扩展临床表现，并强调了 WES 在产前环境中对高回声肾脏进行诊断的效用。
