UNASSIGNED: Nephronophthisis (NPHP) is a rare autosomal recessive inherited tubulointerstitial nephropathy, the most prevalent genetic cause of end-stage renal disease (ESRD) in children. Convincing evidence indicated that the overall prevalence of NPHP in adult-onset ESRD is very likely to be an underestimation. Therefore, understanding the genetic background and clinicopathologic features of adult-onset NPHP is warranted.
UNASSIGNED: we reported one intriguing case with concurrent NPHP3 c.2694-2_2694-1delAG (splicing) variant and c.1082C > G (p.S361C) variant. A 48-year-old male was admitted to our hospital, complained about renal dysfunction for 10 years, and found right renal space-occupying lesion for 1 week. One of the most interesting clinical features is adult-onset ESRD, which differs from previous cases. Another discovery of this study is that the NPHP harboring NPHP3 deletion may be associated with clear cell renal cell carcinoma.
UNASSIGNED: In conclusion, we report two mutations in the NPHP3 gene that cause NPHP with adult-onset ESRD and renal clear cell carcinoma in a Chinese family, enriching the clinical features of NPHP.

This report presents the first case of nodular dermatofibrosis with renal cysts (NDRC) in a beagle. In this atypical case, the gene mutation associated with the disease was not present, the renal cysts showed dynamic changes in size and number, and the patient has greatly surpassed the NDRC life expectation.

Hepatocyte nuclear factor 1β (HNF1β) is essential for biliary development, while its genetic defect triggers the dysplasia of interlobular bile ducts, leading to life-threatening hepatitis and cholestasis. To date, this disorder has mainly been documented in neonates. Here, we report a case of cholestasis in an adult patient caused by a de novo HNF1β mutation. A liver biopsy revealed remarkable shrinkage of the portal area accompanied by a decrease or absence of interlobular bile ducts, veins, and arteries in the portal area. Our case showed that an HNF1β defect could induce late-onset cholestasis with paucity of the portal area in adulthood.

The clinical features of cerebellar vermis hypoplasia, oligophrenia, ataxia, coloboma, and hepatic fibrosis (COACH) characterize the rare autosomal recessive multisystem disorder called COACH syndrome. COACH syndrome belongs to the spectrum of Joubert syndrome and related disorders (JSRDs) and liver involvement distinguishes COACH syndrome from the rest of the JSRD spectrum. Developmental delay and oculomotor apraxia occur early but with time, these can improve and may not be readily apparent or no longer need active medical management. Congenital hepatic fibrosis and renal disease, on the other hand, may develop late, and the temporal incongruity in organ system involvement may delay the recognition of COACH syndrome. We present a case of a young adult presenting late to a Renal Genetics Clinic for evaluation of renal cystic disease with congenital hepatic fibrosis, clinically suspected to have autosomal recessive polycystic kidney disease. Following genetic testing, a reevaluation of his medical records from infancy, together with reverse phenotyping and genetic phasing, led to a diagnosis of COACH syndrome.

Crizotinib is a tyrosine kinase inhibitor that has been found to be effective in the treatment of c-ros oncogene 1-positive non-small cell lung cancer. Although this targeted agent for treating cancer has shown superiority to standard chemotherapy in some ways, this drug has adverse effects, such as the development of renal abscesses. Some associated renal damage may disappear with crizotinib withdrawal. Hence, we present the case of a 58-year-old man with non-small cell lung cancer on crizotinib therapy who developed bilateral renal abnormal space-occupying lesions, successively which were difficult to identify using various imaging methods; even PET-CT highly suspected the right renal masses as malignant. Finally, the right renal lesions were confirmed as renal abscesses by postoperative pathology. The left renal lesion was considered as renal cysts through the lesion disappearing after crizotinib withdrawal. There have been very few reports in this respect, especially proved by various methods and confirmed by postoperative pathology. It is important to recognize this drug-related complication in order to avoid incorrect diagnosis and inadequate therapy. It is necessary to monitor renal changes after taking crizotinib.

Nevoid basal cell carcinoma syndrome (NBCCS) is a rare autosomal dominant-inherited disease characterized by multiple basal cell carcinomas, multiple keratocystic odontogenic tumors, palmar and/or plantar pits. A 50-year-old male patient presented to our hospital with multiple plaques and maculopapular lesions on his face and trunk for more than 20 years. A skin biopsy revealed a number of discrete nests of basaloid cells in the dermis where the peripheral cells are arrayed like a palisade. Multiple odontogenic keratocysts and falx cerebri calcification were found. The diagnosis of NBCCS was made. We treated this patient with 5-aminolevulinic acid photodynamic therapy (ALA-PDT) with red light activation, 5% imiquimod cream and surgical excision for the basal cell carcinomas. All the skin lesions on his face improved substantially after eight sessions of red-light ALA-PDT from clinical observation. Red-light ALA-PDT proved to be a good therapeutic method for NBCCS in this case.

Non-small cell lung cancer patients with anaplastic lymphoma kinase or c-ros oncogene 1 mutations who are treated with the tyrosine kinase inhibitor crizotinib rarely develop crizotinib-associated renal cysts (CARCs). Here, we present a case report and review of the literature supporting the hypothesis that CARCs may correlate positively with progression-free survival.

Polycystic kidney disease with Tuberous sclerosis is a disease caused by the deletions of the TSC2-PKD1 gene. The disease is rarely reported and the characterized manifestation is severe polycystic kidney growth. The diagnosis can be made by molecular analysis. We report the first case of PKDTS discovered in infancy in China with typical neurological and renal manifestations. The patient has infantile spasm, polycystic kidney, skin damage, hypertension, and hematuria after infection. After effective treatment of Rapamycin, the seizures were completely controlled. There was not been any renal function damage in the patient. At the same time, we review the related literature and further elaborate on the variety of clinical manifestations, treatment, and prognosis.

BACKGROUND: paucity of interlobular bile ducts is an important observation at liver biopsy in the diagnostic work-up of neonatal cholestasis. To date, other than in the Alagille syndrome, syndromic paucity of interlobular bile ducts has been documented in four cholestatic neonates with HFN1β mutations. A syndromic phenotype, known as renal cysts and diabetes syndrome (RCAD), has been identified. This is usually characterized by a wide clinical spectrum, including renal cysts, maturity-onset diabetes of the young, exocrine pancreatic insufficiency, urogenital abnormalities and a not well established liver involvement. Herein we report a novel case of paucity of interlobular bile ducts due to an HFN1β defect.
METHODS: A 5-week-old boy was admitted to our department for cholestatic jaundice with increased gamma-glutamyl transpeptidase and an unremarkable clinical examination. He had been delivered by Caesarian section at 38 weeks\' gestation from unrelated parents, with a birth weight of 2600 g (3rd percentile). Screening for cholestatic diseases, including Alagille syndrome, was negative except for a minor pulmonary artery stenosis at echocardiography and a doubt of a thoracic butterfly hemivertebra. The finding of hyperechogenic kidneys with multiple bilateral cortical cysts at ultrasound examination, associated with moderately impaired renal function with proteinuria, polyuria and metabolic acidosis, was suggestive of ciliopathy. A liver biopsy was performed revealing paucity of interlobular bile ducts, thus the diagnosis of Alagille syndrome was reconsidered. Although genetic tests for liver cholestatic diseases were performed with negative results for Alagille syndrome (JAG1 and NOTCH2), a de-novo missense mutation of HNF1β gene was detected. At 18 months of age our patient has persistent cholestasis and his itching is not under satisfactory control.
CONCLUSIONS: Alagille syndrome may not be the only syndrome determining paucity of interlobular bile ducts in neonates presenting with cholestasis and renal impairment, especially in small for gestational age newborns. We suggest that HNF1β deficiency should also be ruled out, taking into consideration HNF1β mutations, together with Alagille syndrome, in next generation sequencing strategies in neonates with cholestasis, renal impairment and/or paucity of interlobular bile ducts at liver biopsy.

Maturity-onset diabetes of the young (MODY) is an autosomal dominant form of early onset diabetes. The hepatocyte nuclear factor-1-beta (HNF1B) gene is responsible for MODY type 5 (MODY5) with distinctive clinical features, including pancreatic atrophy and renal disease. We herein report a Japanese case of young-onset diabetes with typical phenotypes of MODY5 and a novel heterozygous missense mutation (p.L145Q) in the HNF1B gene. The mutation was located in the Pit-Oct-Unc (POU)-specific domain, and the amino acid residue L145 was highly conserved among species. It is strongly suggested that this mutation explains the phenotypes of MODY5.