BACKGROUND: Autosomal recessive polycystic kidney disease (ARPKD) is a rare inherited cystic disease characterized by bilateral renal cyst formation and congenital liver fibrosis. Cardiovascular disorders such as noncompaction of ventricular myocardium (NVM) have not been reported with ARPKD.
METHODS: A 5-month-old girl was examined after presenting with a fever and turbid urine for one day and was diagnosed as urinary tract infection. Urinary ultrasound showed multiple round, small cysts varying in size in both kidneys. Genetic testing revealed two heterozygous mutations and one exon deletion in the polycystic kidney and hepatic disease 1 gene, indicating a diagnosis of ARPKD. During hospitalization, she was found to have chronic heart failure after respiratory tract infection, with an ejection fraction of 29% and fraction shortening of 13%. When the patient was 15 months old, it was found that she had prominent trabeculations and deep intertrabecular recesses with the appearance of blood flow from the ventricular cavity into the intertrabecular recesses by echocardiography. The noncompaction myocardium was 0.716 cm and compaction myocardium was 0.221 cm (N/C = 3.27), indicating a diagnosis of NVM. Liver and kidney function remained normal during four-year follow-up.
CONCLUSIONS: This is the first report of NVM in a patient with ARPKD. It is unsure if the coexistence of NVM and ARPKD is a coincidence or they are different manifestations of ciliary dysfunction in the heart and kidneys.

Serving as the cell\'s sensory antennae, primary cilia are linked to numerous human genetic diseases when they malfunction. DZIP1L, identified as one of the genetic causes of human autosomal recessive polycystic kidney disease (ARPKD), is an evolutionarily conserved ciliary basal body protein. Although it has been reported that DZIP1L is involved in the ciliary entry of PKD proteins, the underlying mechanism remains elusive. Here, an uncharacterized role of DZIP1L is reported in modulating the architecture and function of transition fibers (TFs), striking ciliary base structures essential for selective cilia gating. Using C. elegans as a model, C01G5.7 (hereafter termed DZIP-1) is identified as the sole homolog of DZIP1L, which specifically localizes to TFs. While DZIP-1 or ANKR-26 (the ortholog of ANKRD26) deficiency shows subtle impact on TFs, co-depletion of DZIP-1 and ANKR-26 disrupts TF assembly and cilia gating for soluble and membrane proteins, including the ortholog of ADPKD protein polycystin-2. Notably, the synergistic role for DZIP1L and ANKRD26 in the formation and function of TFs is highly conserved in mammalian cilia. Hence, the findings illuminate an evolutionarily conserved role of DZIP1L in TFs architecture and function, highlighting TFs as a vital part of the ciliary gate implicated in ciliopathies ARPKD.

BACKGROUND: The disease of Caroli is a rare congenital disorder, characterized by the dilated intrahepatic bile ducts, resulting from mutations in the PKHD1 gene. Caroli syndrome, characterized by dilated intrahepatic bile ducts with congenital hepatic fibrosis, is linked to autosomal recessive polycystic kidney disease. The clinical manifestations of Caroli disease are not typical, and Caroli disease is easy to be missed and misdiagnosed. Therefore, we reported this case in the hope of raising awareness of the disease among clinicians.
METHODS: The clinical manifestation of a 10-year-old girl was subcutaneous hemorrhage.
METHODS: Magnetic resonance imaging (MRI ) indicates that the person may have Caroli disease, cirrhosis, splenomegaly, portal hypertension, esophagogastric fundal varices, or sponge kidneys.
METHODS: The patient was advised for liver transplantation.
RESULTS: The patient parents did not take our treatment advice, and they asked to go to a better hospital for further treatment, so we did not give the patient any treatment.
CONCLUSIONS: This case serves as a reminder that if we encounter a patient with hemophilia in our clinic, we should not only consider hematologic diseases and cirrhosis, but also perform an epigastric MRI and magnetic resonance cholangiopancreatography to rule out Caroli disease.

常染色体隐性遗传多囊肾病（ARPKD）是累及肾脏和肝脏的罕见纤毛病之一，也是儿童慢性肾脏病（CKD）的常见原因之一。尚缺乏针对ARPKD的特异性治疗方法，故了解其机制至关重要。信号通路异常激活、调节因子和细胞因子的异常分泌、细胞外基质重塑、细胞极性和机械性质的改变等相关机制逐渐被认识。尽管ARPKD的遗传基础是明确的，但对ARPKD的变异基因及其表达蛋白的确切功能和囊肿形成的关键分子机制的认识仍不足，相关信号通路的具体机制也不完全清楚。为了加强对ARPKD的认识，寻找临床上特异的治疗药物，对该病的致病机制进行综述。.

OBJECTIVE: To explore the clinical characteristics and molecular pathogenesis of a child with autosomal dominant polycystic kidney disease (ARPKD).
METHODS: Prenatal ultrasound, clinical feature and family history of the child were analyzed. Whole exome sequencing was carried out for the child. Candidate variants were verified by Sanger sequencing.
RESULTS: The child has featured premature birth with very low weight, neonatal respiratory distress, metabolic acidosis, and congenital nephrotic syndrome. Gene sequencing revealed that he has harbored compound heterozygous variants of the PKHD1 gene (NM_138694), including c.3885T>A (p.Tyr1295*) in exon 32 and c.7812_7816dupTGATA (p.Thr2606Metfs*63) in exon 49, which were respectively inherited from his mother and father.
CONCLUSIONS: The compound heterozygous variants of the PKHD1 gene probably underlay the disease in this child.

暂无摘要。

Autosomal recessive polycystic kidney disease is a hereditary fibrocystic disease that involves the kidneys and biliary tract. Its major histological presentations are the fusiform dilatation of renal collecting ducts and the malformation of the hepatobiliary ductal plate. We isolated peripheral blood mononuclear cells from a 21-year-old adult female patient carrying a homozygous p.L2665P mutation in the PKHD1 gene and used nonintegrated exogenous in vitro differentiation vectors for reprogramming to obtain human induced pluripotent stem cells. The induced pluripotent stem cells thus established had a normal karyotype, expressed markers of pluripotency, and could differentiate into three germ layers in the body.

OBJECTIVE: To explore the genetic basis for a fetus featuring infantile polycystic kidney disease (IPKD).
METHODS: Following elective abortion, fetal tissue and peripheral blood samples of its parents were collected for the extraction of genomic DNA. Whole exome sequencing was carried out to detect potential variants correlated with the phenotype.
RESULTS: The fetus was found to harbor a heterozygous c.1370C>T (p.P457L) variant of the HNF1B gene, which was unreported previously. The same variant was not detected in either parent.
CONCLUSIONS: The heterozygous c.1370C>T (p.P457L) variant of the HNF1B gene probably underlay the IPKD in this fetus. Above finding has enabled genetic counseling and prenatal diagnosis for the family.

OBJECTIVE: To explore the genetic etiology of a fetus with autosomal recessive polycystic kidney disease (ARPKD).
METHODS: Prenatal ultrasonography has revealed oligohydramnios and abnormal structure of fetal kidneys. After careful counseling, the couple opted induced abortion. With informed consent, genomic DNA was extracted from the muscle sample of the abortus and peripheral blood samples of the couple. High throughput whole exome sequencing was carried out to detect potential variants in relation with the disease. Suspected variants were verified by Sanger sequencing.
RESULTS: Prenatal ultrasound revealed increased size of fetal kidneys, with multiple hyperechos from the right kidney, and multiple hyperechos with anechoic masses within the left kidney. DNA sequencing revealed that the fetus has carried heterozygous variants of the PKHD1 gene, including c.7994T>C inherited from its father, and two heterozygous variants of the PKHD1 gene c.5681G>A from its mother.
CONCLUSIONS: The compound heterozygous c.7994T>C and c.5681G>A variants of the PKHD1 gene probably underlay the pathogenesis of ARPKD in this fetus. Above results can provide guidance for subsequent pregnancies of the couple.

OBJECTIVE: To explore the genetic basis for a fetus with renal abnormalities through whole exome sequencing and imaging examination.
METHODS: Clinical data and result of medical imaging of the fetus was collected. Amniotic fluid sample was collected for the extraction of fetal DNA. Whole exome sequencing was carried out. Candidate variants were verified by Sanger sequencing.
RESULTS: Prenatal ultrasonography showed that the fetus had bilateral enlargement of the kidneys with hyperechogenicity and diffuse renal cysts. Whole exome sequencing revealed that the fetus carried compound heterozygous variants of the PKHD1 gene, namely c.5137G>T and c.2335_2336delCA, which were derived from its mother and father, respectively.
CONCLUSIONS: The fetus was diagnosed with autosomal recessive polycystic kidney disease through combined prenatal ultrasonography and whole exome sequencing. The compound heterozygous variants of the PKHD1 gene probably underlay the pathogenesis in the fetus. The results have enabled prenatal diagnosis and genetic counseling for its parents.