PAX2是在眼睛胚胎发育过程中表达的转录因子,耳朵,CNS,和泌尿生殖道,是肾脏发育的主要调节因子之一。该基因的突变与乳头状肾综合征(PAPRS)有关,一种以视神经发育不良和肾脏发育不良为特征的遗传性疾病。在过去的28年里,许多队列研究和病例报告强调了PAX2参与大范围的肾脏畸形和疾病,有或没有眼睛异常,将与PAX2变体相关的表型定义为“PAX2相关疾病”。这里,我们报告了两个新的序列变异,并回顾了LeidenOpenVariationDatabase3.0上注释的PAX2突变.从53例先天性肾脏和泌尿道异常(CAKUT)的儿科患者的外周血中提取DNA。用Sanger技术对PAX2基因编码外显子和侧翼内含子区进行测序。观察到两名无关患者和两名双胞胎携带一个已知和两个未知的PAX2变异。该队列中PAX2相关疾病的发生率为5.8%,考虑所有CAKUT表型(PAPRS表型为16.7%,非综合征型CAKUT为2.5%)。尽管PAX2突变在PAPRS或非综合征性肾发育不全患者中频率较高,根据迄今为止在LOVD3中报道的变异体的综述,在具有其他CAKUT表型的儿科患者中检测到PAX2相关疾病.在我们的研究中,只有一名患者患有无眼部表型的CAKUT,但他的双胞胎有肾脏和眼部受累,证实了极端的家族间和家族内表型变异性。
PAX2 is a transcription factor expressed during embryogenesis in the eye, ear, CNS, and genitourinary tract, and is one of the major regulators of kidney development. Mutations in this gene are associated with papillorenal syndrome (PAPRS), a genetic condition characterized by optic nerve dysplasia and renal hypo/dysplasia. In the last 28 years, many cohort studies and case reports highlighted PAX2\'s involvement in a large spectrum of kidney malformations and diseases, with or without eye abnormalities, defining the phenotypes associated with PAX2 variants as \"PAX2-related disorders\". Here, we reported two new sequence variations and reviewed PAX2 mutations annotated on the Leiden Open Variation Database 3.0. DNA was extracted from the peripheral blood of 53 pediatric patients with congenital abnormalities of the kidney and urinary tract (CAKUT). PAX2 gene-coding exonic and flanking intronic regions were sequenced with Sanger technology. Two unrelated patients and two twins carrying one known and two unknown PAX2 variations were observed. The frequency of PAX2-related disorders in this cohort was 5.8%, considering all CAKUT phenotypes (16.7% in the PAPRS phenotype and 2.5% in non-syndromic CAKUT). Although PAX2 mutations have a higher frequency in patients with PAPRS or non-syndromic renal hypoplasia, from the
review of variants reported to date in LOVD3, PAX2-related disorders are detected in pediatric patients with other CAKUT phenotypes. In our study, only one patient had a CAKUT without an ocular phenotype, but his twin had both renal and ocular involvement, confirming the extreme inter- and intrafamilial phenotypic variability.