■常染色体隐性多囊肾病(ARPKD),一种以肾囊肿为特征的罕见遗传病,显示复杂的临床和遗传异质性。本研究旨在探索科威特ARPKD的遗传景观,并研究其基因与临床表现之间的复杂关系,以增强我们的理解并为更有效的ARPKD管理策略做出贡献。
这项研究招募了来自科威特44个不同家庭的60名疑似ARPKD患者。参与者来自不同种族,年龄0-70岁。此外,33是男性,15是女性,12人由于先天性异常而性别不确定。收集综合临床资料。通过下一代全外显子组测序鉴定突变,并使用Sanger测序确认突变。
■在60例ARPKD疑似病例中,20人(33.3%)在出生后数小时或出生后第一个月结束时死亡,1人(1.7%)在出生后12个月内死亡。其余39例(65.0%)存活,在研究的时候,并表现出与ARPKD相关的多种临床特征,包括系统性高血压(5.0%),肺发育不全(11.7%),变形特征(40.0%),心脏问题(8.3%),囊性肝(5.0%),波特综合症(13.3%),发育迟缓(8.3%),囊性肾脏增大(100%)。12个突变,包括新的截断突变,在17/44个家庭(38.6%)的31/60例(51.7%)中发现。此外,8/12(66.7%)突变发生在PKHD1基因,剩下的四个基因:NPHP3,VPS13P,CC2D2A,ZNF423。
■本研究强调了科威特ARPKD患者的临床特征和基因突变谱。它强调了个性化方法来改善ARPKD诊断和治疗的必要性,提供管理ARPKD的关键见解。
UNASSIGNED: Autosomal recessive polycystic kidney disease (ARPKD), a rare genetic disorder characterized by kidney cysts, shows complex clinical and genetic heterogeneity. This study aimed to explore the genetic landscape of ARPKD in Kuwait and examine the intricate relationship between its genes and clinical presentation to enhance our understanding and contribute towards more efficient management strategies for ARPKD.
UNASSIGNED: This study recruited 60 individuals with suspected ARPKD from 44 different families in Kuwait. The participants were of different ethnicities and aged 0-70 years. Additionally, 33 were male, 15 were female, and 12 had indeterminant sex due to congenital anomalies. Comprehensive clinical data were collected. Mutations were identified by next-generation whole exome sequencing and confirmed using Sanger sequencing.
UNASSIGNED: Of the 60 suspected ARPKD cases, 20 (33.3 %) died within hours of birth or by the end of the first month of life and one (1.7 %) within 12 months of birth. The remaining 39 (65.0 %) cases were alive, at the time of the study, and exhibited diverse clinical features related to ARPKD, including systematic hypertension (5.0 %), pulmonary hypoplasia (11.7 %), dysmorphic features (40.0 %), cardiac problems (8.3 %), cystic liver (5.0 %), Potter syndrome (13.3 %), developmental delay (8.3 %), and enlarged cystic kidneys (100 %). Twelve mutations, including novel truncating mutations, were identified in 31/60 cases (51.7 %) from 17/44 families (38.6 %). Additionally, 8/12 (66.7 %) mutations were in the
PKHD1 gene, with the remaining four in different genes: NPHP3, VPS13P, CC2D2A, and ZNF423.
UNASSIGNED: This study highlights the spectrum of clinical features and genetic mutations of patients with ARPKD in Kuwait. It highlights the necessity for personalized approaches to improve ARPKD diagnosis and treatment, offering crucial insights into managing ARPKD.