Xu Fengdan, Peng Qi, He Xiaoguang, Chen Xiaolan, Jiang Shuanglan, Lu Xiaomei, Li Ning
Department of Neonatology, Guangdong Medical University Affiliated Dongguan Children's Hospital, Dongguan, China.
Department of Medical and Molecular Genetics, Dongguan Institute of Pediatrics, Dongguan, China.
Front Pediatr. 2022 Nov 15;10:1020536. doi: 10.3389/fped.2022.1020536. eCollection 2022.
Here, we report the case of an infant suffering from Alagille syndrome (ALGS), manifesting with the atypical clinical manifestations of prenatal oligohydramnios and renal lesions. To the best of our knowledge, this is the first case of ALGS presenting as prenatal oligohydramnios and renal lesions caused by a variant of the 2 gene.
A 3-month-old male infant was hospitalized for severe malnutrition. He presented with prenatal oligohydramnios from 28 weeks of gestation. After birth, he failed to thrive and suffered from impaired motor development, thermoregulation disorders, congenital bilateral renal hypodysplasia, which initially manifested as stage 5 before improving to stage 3 chronic renal impairment, slightly elevated levels of transaminases, cholestasis, and dysmorphic facial features. We used a diagnostic screening panel of 4,047 pathogenic genes and whole exome sequencing (WES) to analyze the proband and his parents (who had normal kidneys). We found that the proband carried a heterozygous splicing variant (c.5930-2A > G) in intron 33 of the 2 gene. Transcriptome sequencing confirmed that the mutation of this gene site would affect the splicing of NOTCH2 mRNA and lead to exon 33 skipping.
Our case expands the spectrum of pathogenic variants of the 2 gene that are known to be associated with ALGS and characterized by prenatal oligohydramnios and renal lesions. It also reminds us of the necessity to monitor the liver and kidney function of the infant if a mother has oligohydramnios during pregnancy and we recommend ALGS as an additional differential diagnosis in prenatal renal abnormalities.
在此，我们报告一例患有阿拉吉列综合征（ALGS）的婴儿病例，该婴儿表现出产前羊水过少和肾脏病变等非典型临床表现。据我们所知，这是首例由JAG1基因变异导致以产前羊水过少和肾脏病变为表现的ALGS病例。
一名3个月大的男婴因严重营养不良住院。他自妊娠28周起出现产前羊水过少。出生后，他生长发育迟缓，存在运动发育障碍、体温调节紊乱、先天性双侧肾发育不全，最初表现为5期，后改善为3期慢性肾功能损害，转氨酶水平略有升高、胆汁淤积以及面部畸形特征。我们使用包含4047个致病基因的诊断筛查面板和全外显子测序（WES）对先证者及其父母（其肾脏正常）进行分析。我们发现先证者在JAG1基因第33内含子中携带一个杂合剪接变异（c.5930-2A＞G）。转录组测序证实该基因位点的突变会影响NOTCH2 mRNA的剪接并导致第33外显子跳跃。
我们的病例拓宽了已知与ALGS相关且以产前羊水过少和肾脏病变为特征的JAG1基因致病变异谱。它还提醒我们，如果母亲在孕期出现羊水过少，有必要监测婴儿的肝肾功能，并且我们建议将ALGS作为产前肾脏异常的一个额外鉴别诊断。
