未经批准:这里,我们报告了一名患有Alagille综合征(ALGS)的婴儿的病例,表现为产前羊水过少和肾脏病变的不典型临床表现。据我们所知,这是首例ALGS表现为产前羊水过少和由NOTCH2基因的从头变异引起的肾脏病变。
未经评估:一名3个月大的男婴因严重营养不良住院。他在妊娠28+4周时出现了产前羊水过少。出生后,他未能茁壮成长,运动发育受损,体温调节障碍,先天性双侧肾发育不良,最初表现为5期,然后改善为3期慢性肾功能损害,转氨酶水平略有升高,胆汁淤积,和畸形的面部特征。我们使用了4,047个致病基因和全外显子组测序(WES)的诊断筛选小组来分析先证者及其父母(肾脏正常)。我们发现先证者在NOTCH2基因的内含子33中携带一个从头杂合剪接变体(c.5930-2A>G)。转录组测序证实,该基因位点的突变会影响NOTCH2mRNA的剪接并导致外显子33跳跃。
UNASSIGNED:我们的案例扩展了已知与ALGS相关的NOTCH2基因的致病变异谱,其特征是产前羊水过少和肾脏病变。它还提醒我们,如果母亲在怀孕期间羊水过少,则必须监测婴儿的肝肾功能,我们建议ALGS作为产前肾脏异常的额外鉴别诊断。
UNASSIGNED: 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 de novo variant of the NOTCH2 gene.
UNASSIGNED: A 3-month-old male infant was hospitalized for severe malnutrition. He presented with prenatal oligohydramnios from 28+4 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 de novo heterozygous splicing variant (c.5930-2A > G) in intron 33 of the NOTCH2 gene. Transcriptome sequencing confirmed that the mutation of this gene site would affect the splicing of NOTCH2 mRNA and lead to exon 33 skipping.
UNASSIGNED: Our
case expands the spectrum of pathogenic variants of the NOTCH2 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.