Abstract：
The co-occurrence of pathogenic variants has emerged as a relatively common finding underlying complex phenotypes. Here, we used whole-exome sequencing (WES) to solve an unclassified multisystem clinical presentation.
A 20-year-old woman affected by moderate intellectual disability (ID), dysmorphic features, hypertrichosis, scoliosis, recurrent bronchitis, and pneumonia with bronchiectasis, colelithiasis, chronic severe constipation, and a family history suggestive of autosomal dominant recurrence of polycystic kidney disease was analyzed by WES to identify the genomic events underlying the condition.
Four co-occurring genomic events fully explaining the proband\'s clinical features were identified. A de novo truncating USP7 variant was disclosed as the cause of Hao-Fountain syndrome, a disorder characterized by syndromic ID and distinctive behavior. Compound heterozygosity for a major cystic fibrosis-causing variant and the modulator allele, IVS8-5T, in CFTR explained the recurrent upper and lower respiratory way infections, bronchiectasis, cholelithiasis, and chronic constipation. Finally, a truncating PKD2 variant co-segregating with polycystic kidney disease in the family allowed presymptomatic disease diagnosis.
The co-occurring variants in USP7 and CFTR variants explained the multisystem disorder of the patient. The comprehensive dissection of the phenotype and early diagnosis of autosomal dominant polycystic kidney disease allowed us to manage the CFTR-related disorder symptoms and monitor renal function and other complications associated with PKD2 haploinsufficiency, addressing proper care and surveillance.
A 20-year-old woman affected by moderate intellectual disability (ID), dysmorphic features, hypertrichosis, scoliosis, recurrent bronchitis, and pneumonia with bronchiectasis, colelithiasis, chronic severe constipation, and a family history suggestive of autosomal dominant recurrence of polycystic kidney disease was analyzed by WES to identify the genomic events underlying the condition.
Four co-occurring genomic events fully explaining the proband\'s clinical features were identified. A de novo truncating USP7 variant was disclosed as the cause of Hao-Fountain syndrome, a disorder characterized by syndromic ID and distinctive behavior. Compound heterozygosity for a major cystic fibrosis-causing variant and the modulator allele, IVS8-5T, in CFTR explained the recurrent upper and lower respiratory way infections, bronchiectasis, cholelithiasis, and chronic constipation. Finally, a truncating PKD2 variant co-segregating with polycystic kidney disease in the family allowed presymptomatic disease diagnosis.
The co-occurring variants in USP7 and CFTR variants explained the multisystem disorder of the patient. The comprehensive dissection of the phenotype and early diagnosis of autosomal dominant polycystic kidney disease allowed us to manage the CFTR-related disorder symptoms and monitor renal function and other complications associated with PKD2 haploinsufficiency, addressing proper care and surveillance.
摘要：
致病变体的共同出现已经成为潜在复杂表型的相对常见的发现。这里,我们使用全外显子组测序(WES)来解决未分类的多系统临床表现.
一名20岁女性患有中度智力障碍（ID），变形特征，多毛症,脊柱侧弯,复发性支气管炎,肺炎和支气管扩张，结石症,慢性严重便秘，通过WES分析提示多囊肾疾病常染色体显性遗传复发的家族史,以确定该疾病背后的基因组事件.
确定了四个共同发生的基因组事件，完全解释了先证者的临床特征。从头截断USP7变体被公开为Hao-Fountain综合征的原因，一种以综合征ID和独特行为为特征的疾病。主要囊性纤维化引起变异体和调节等位基因的复合杂合性，IVS8-5T,在CFTR中解释了反复发生的上呼吸道和下呼吸道感染，支气管扩张,胆石症,和慢性便秘.最后,在家族中与多囊肾疾病共同隔离的截短PKD2变异体允许对症前疾病诊断.
USP7和CFTR变体中共同出现的变体解释了患者的多系统疾病。表型的全面解剖和常染色体显性多囊肾病的早期诊断使我们能够管理CFTR相关的疾病症状，监测肾功能和其他与PKD2单倍体功能不全相关的并发症。解决适当的护理和监视。
一名20岁女性患有中度智力障碍（ID），变形特征，多毛症,脊柱侧弯,复发性支气管炎,肺炎和支气管扩张，结石症,慢性严重便秘，通过WES分析提示多囊肾疾病常染色体显性遗传复发的家族史,以确定该疾病背后的基因组事件.
确定了四个共同发生的基因组事件，完全解释了先证者的临床特征。从头截断USP7变体被公开为Hao-Fountain综合征的原因，一种以综合征ID和独特行为为特征的疾病。主要囊性纤维化引起变异体和调节等位基因的复合杂合性，IVS8-5T,在CFTR中解释了反复发生的上呼吸道和下呼吸道感染，支气管扩张,胆石症,和慢性便秘.最后,在家族中与多囊肾疾病共同隔离的截短PKD2变异体允许对症前疾病诊断.
USP7和CFTR变体中共同出现的变体解释了患者的多系统疾病。表型的全面解剖和常染色体显性多囊肾病的早期诊断使我们能够管理CFTR相关的疾病症状，监测肾功能和其他与PKD2单倍体功能不全相关的并发症。解决适当的护理和监视。
