Xu Suhua, Hu Lan, Yang Lin, Wu Bingbing, Cao Yun, Zhang Rong, Xu Xin, Ma Haiyan, Zhou Wenhao, Cheng Guoqiang, Zhang Peng, Hu Liyuan
Department of Neonatology, National Children's Medical Center, Children's Hospital of Fudan University, Shanghai, China.
Clinical Genetic Center, National Children's Medical Center, Children's Hospital of Fudan University, Shanghai, China.
Front Pediatr. 2022 Jun 17;10:899991. doi: 10.3389/fped.2022.899991. eCollection 2022.
Galloway-Mowat syndrome type 3 (GAMOS3) is an extremely rare and severe autosomal-recessive disease characterized by early-onset nephrotic syndrome (NS), microcephaly and neurological impairment. Reported GAMOS cases have gradually increased since pathogenic variants were identified as the aetiology in 2017.
Using whole-exome sequencing and a data analysis process established by Children's Hospital of Fudan University, the clinical and molecular features of 3 infants with mutations were summarized. Literature regarding the clinical features of GAMOS3 caused by variants was reviewed.
Thirty-seven individuals (3 from this study) from 34 families were included. Twenty-two different variants were identified. The c.740G>A (p.Arg247Gln) variant in was detected in 15 families (44%), all from Asia. Most affected individuals (including patients I and II in this study) showed a typical phenotype, including microcephaly (92%) with brain anomalies (97%), developmental delay (81%), congenital NS (54%), and craniofacial (94%) and skeletal dysmorphism (84%). Renal manifestations varied from proteinuria (94%, median onset = 1.5 months) to NS (83%) and end-stage renal disease (48%, 11 months) during follow-up. Patients with congenital NS had a lower survival probability (median survival time = 3 months) than those without congenital NS (78 months) ( < 0.01, log-rank test).
GAMOS3 is a progressive renal-neurological syndrome with a poor prognosis, especially with congenital NS. Microcephaly with dysmorphic features are vital clues to further evaluate renal impairment and brain anomalies. Timely molecular diagnosis is crucial for clinical decision-making, appropriate treatment and genetic counselling.
3型加洛韦 - 莫瓦特综合征（GAMOS3）是一种极其罕见且严重的常染色体隐性疾病，其特征为早发性肾病综合征（NS）、小头畸形和神经功能障碍。自2017年致病变异被确定为病因以来，报道的GAMOS病例逐渐增多。
采用全外显子组测序以及复旦大学附属儿科医院建立的数据分析流程，总结了3例有突变婴儿的临床和分子特征。回顾了关于由变异导致的GAMOS3临床特征的文献。
纳入了来自34个家庭的37例个体（本研究中的3例）。鉴定出22种不同的变异。在15个家庭（44%）中检测到基因中的c.740G>A（p.Arg247Gln）变异，所有这些家庭均来自亚洲。大多数受累个体（包括本研究中的患者I和II）表现出典型的表型，包括小头畸形（92%）伴脑异常（97%）、发育迟缓（81%）、先天性肾病综合征（54%）以及颅面部（94%）和骨骼畸形（84%）。在随访期间，肾脏表现从蛋白尿（94%，中位发病时间 = 1.5个月）到肾病综合征（83%）和终末期肾病（48%，11个月）不等。患有先天性肾病综合征的患者的生存概率（中位生存时间 = 3个月）低于无先天性肾病综合征的患者（78个月）（P<0.01，对数秩检验）。
GAMOS3是一种预后不良的进行性肾 - 神经综合征，尤其是伴有先天性肾病综合征时。具有畸形特征的小头畸形是进一步评估肾功能损害和脑异常的重要线索。及时的分子诊断对于临床决策、适当治疗和遗传咨询至关重要。
