Clinical and genetic variability of PAX2-related disorder in the Japanese population.,Journal of Human Genetics

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Clinical and genetic variability of PAX2-related disorder in the Japanese population.
Journal of Human Genetics ( IF 2.6 ) Pub Date : 2020-03-16 , DOI: 10.1038/s10038-020-0741-y
Rini Rossanti ₁ , Naoya Morisada _{1,

2} , Kandai Nozu ₁ , Koichi Kamei ₃ , Tomoko Horinouchi ₁ , Tomohiko Yamamura ₁ , Shogo Minamikawa _{1,

4} , Junya Fujimura _{1,

5} , China Nagano ₁ , Nana Sakakibara ₁ , Takeshi Ninchoji ₁ , Hiroshi Kaito _{1,

6} , Shuichi Ito _{3,

7} , Ryojiro Tanaka _{4,

6} , Kazumoto Iijima ₁

Affiliation

Pathogenic variants of paired box gene 2 (PAX2) cause autosomal-dominant PAX2-related disorder, which includes renal coloboma syndrome (RCS). Patients with PAX2-related disorder present with renal and ophthalmological pathologies, as well as with other abnormalities, including developmental problems and hearing loss. We sequenced PAX2 in 457 patients with congenital anomalies of the kidney and urinary tract or with renal dysfunction of unknown cause and identified 19 different pathogenic variants in 38 patients from 30 families (6.5%). Thirty-four patients had renal hypodysplasia or chronic kidney disease of unknown cause, and three had focal segmental glomerulosclerosis. Although no obvious genotype-phenotype correlation was observed, six of the seven patients who developed end-stage renal disease in childhood had truncating variants. Twenty-three patients had ocular disabilities, mostly optic disc coloboma. Non-renal and non-ophthalmological manifestations included developmental disorder, electrolyte abnormality, and gonadal abnormalities. Two unrelated patients had congenital cystic adenomatoid malformations in their lungs. Six of ten probands with PAX2 mutation identified by next-generation sequencing did not show typical RCS manifestations. We conclude that PAX2-related disorder has a variable clinical presentation and can be diagnosed by next-generation sequencing even in the absence of typical RCS manifestations.

中文翻译：

日本人群中PAX2相关疾病的临床和遗传变异性。

配对盒基因2（PAX2）的致病变异导致常染色体显性PAX2相关疾病，包括肾小球瘤综合征（RCS）。患有PAX2相关疾病的患者表现出肾脏和眼科疾病以及其他异常，包括发育问题和听力下降。我们对457例先天性肾脏和泌尿道异常或原因不明的肾功能不全的患者进行了PAX2测序，并从30个家庭（6.5％）的38例患者中鉴定出19种不同的致病变异。三十四例患有肾发育不全或原因不明的慢性肾脏疾病，三例患有局灶性节段性肾小球硬化。尽管未观察到明显的基因型与表型相关性，但在儿童期发展为终末期肾脏疾病的七名患者中，有六名具有截短变异。23例患有眼部残疾，多数为视盘性圆盘状结肠癌。非肾脏和非眼科表现包括发育障碍，电解质异常和性腺异常。两名不相关的患者的肺部患有先天性囊性腺瘤样畸形。通过下一代测序鉴定出的十个具有PAX2突变的先证者中有六个没有显示出典型的RCS表现。我们得出的结论是，即使没有典型的RCS表现，PAX2相关疾病的临床表现也各不相同，并且可以通过下一代测序来诊断。两名不相关的患者的肺部患有先天性囊性腺瘤样畸形。通过下一代测序鉴定出的十个具有PAX2突变的先证者中有六个没有显示出典型的RCS表现。我们得出的结论是，即使没有典型的RCS表现，PAX2相关疾病的临床表现也各不相同，并且可以通过下一代测序来诊断。两名不相关的患者的肺部患有先天性囊性腺瘤样畸形。通过下一代测序鉴定出的十个具有PAX2突变的先证者中有六个没有显示出典型的RCS表现。我们得出的结论是，即使没有典型的RCS表现，PAX2相关疾病的临床表现也各不相同，并且可以通过下一代测序来诊断。

更新日期：2020-04-24

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