A case report of a Filipino boy with childhood cataract and clinically diagnosed Roberts Syndrome

@#Childhood cataract is a common cause of visual impairment. Familial types are uncommon among Filipinos. Furthermore, it is not common to have one that follows an autosomal dominant pattern of inheritance but with associated syndromic presentation like Roberts syndrome which is an autosomal recessive disorder. This is a case of a 9-year-old Filipino boy with cataract in the left eye associated with low-set ears, facial asymmetry, underdeveloped nasal ala, cleft lip and palate, macroglossia, micrognathia, short right shin, and absent feet. Patient was clinically diagnosed with Roberts syndrome. We present a clinically diagnosed Roberts syndrome (RS), the first reported RS in a Filipino in local and international literature to our knowledge with an autosomal dominant childhood cataract. Genetic testing can assist in the confirmation of this case.

Splicing mutations of GSDME cause late-onset non-syndromic hearing loss / 临床耳鼻咽喉头颈外科杂志

Objective:To dentify the genetic and audiological characteristics of families affected by late-onset hearing loss due to GSDMEgene mutations, aiming to explore clinical characteristics and pathogenic mechanisms for providing genetic counseling and intervention guidance. Methods:Six families with late-onset hearing loss from the Chinese Deafness Genome Project were included. Audiological tests, including pure-tone audiometry, acoustic immittance, speech recognition scores, auditory brainstem response, and distortion product otoacoustic emission, were applied to evaluate the hearing levels of patients. Combining with medical history and physical examination to analyze the phenotypic differences between the probands and their family members. Next-generation sequencing was used to identify pathogenic genes in probands, and validations were performed on their relatives by Sanger sequencing. Pathogenicity analysis was performed according to the American College of Medical Genetics and Genomics Guidelines. Meanwhile, the pathogenic mechanisms of GSDME-related hearing loss were explored combining with domestic and international research progress. Results:Among the six families with late-onset hearing loss, a total of 30 individuals performed hearing loss. The onset of hearing loss in these families ranged from 10 to 50 years（mean age: 27.88±9.74 years）. In the study, four splicing mutations of the GSDME were identified, including two novel variants: c. 991－7C>G and c. 1183+1G>T. Significantly, the c. 991－7C>G was a de novo variant. The others were previously reported variants: c. 991-1G>C and c. 991-15_991-13del, the latter was identified in three families. Genotype-phenotype correlation analysis revealed that probands with the c. 991－7C>G and c. 1183+1G>T performed a predominantly high-frequency hearing loss. The three families carrying the same mutation exhibited varying degrees of hearing loss, with an annual rate of hearing deterioration exceeding 0.94 dB HL/year. Furthermore, follow-up of interventions showed that four of six probands received intervention（66.67%）, but the results of intervention varied. Conclusion:The study analyzed six families with late-onset non-syndromic hearing loss linked to GSDME mutations, identifying four splicing variants. Notably, c. 991－7C>G is the first reported de novo variant of GSDME globally. Audiological analysis revealed that the age of onset generally exceeded 10 years,with variable effectiveness of interventions.

Advances in the regulation of autosomal dominant polycystic kidney disease by Hippo signaling pathway / 中华肾脏病杂志

The Hippo signaling pathway is highly conserved in evolution, and participates in the regulation of cell proliferation, differentiation, and tissular dynamic balance, and plays an important role in regulating tissue, organ size, and cell number. Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disease and one of the most common causes of end-stage renal disease. Emerging studies have identified the Hippo signaling pathway is closely related to the occurrence and development of ADPKD. The abnormal activity and expression of the main members of the pathway affect the cilia and cell polarity of renal tubular epithelial cells and induce the formation of renal cysts. The review summarizes the potential mechanism of the Hippo pathway in the pathogenesis of ADPKD, the crosstalk with other signaling pathways, and the variances in different species, and discusses the strategies for the treatment of ADPKD based on the Hippo signaling pathway to provide new strategies for the treatment.

Deciphering the pathogenicity of COL4A4 heterozygous splicing mutations and the genotype-phenotype correlation in autosomal dominant Alport syndrome / 中华肾脏病杂志

Objective:Through the investigation of the pathogenicity of COL4A4 heterozygous splicing mutations and the genotype-phenotype correlation in autosomal dominant Alport syndrome (ADAS), to better understand the impact of COL4A4 heterozygous splicing mutations on ADAS. Methods:The study was a case series analysis. Patients from 5 ADAS families with COL4A4 heterozygous splicing mutations detected by whole exome sequencing were recruited by three hospitals. In vivo transcriptional analysis and/or in vitro minigene splicing assay were conducted to determine the splicing patterns and assess the pathogenicity of COL4A4 heterozygous splicing mutations. Results:In the five ADAS pedigrees carrying COL4A4 heterozygous splicing mutations, four novel ADAS splicing patterns were described. In pedigree 1-4, most patients presented with continuous hematuria or/and microalbuminuria. Otherwise,the proband in pedigree 4 presented with macroalbuminuria and the proband in pedigree 1 had progressed to chronic kidney disease stage 2 at the age of 70 years old. In pedigree 5, all patients developed end-stage renal disease between 28 and 41 years old. c.735+3A>G detected in pedigree 1 and pedigree 2 and c.694-1G>C detected in pedigree 3 both led to exon 12 skipping in COL4A4, resulting in 42 nucleotides in-frame deletion (c.694_735del). c.2056+3A>G detected in pedigree 4 led to COL4A4 exon 26 skipping, which caused in-frame deletion of 69 nucleotides (c.1988_2056del). c.2716+5G>T detected in pedigree 5 led to a 360 nucleotides large in-frame deletion, including 100 bp sequence at the 3'end of exon 29,the whole sequence of exon 30 and 89 bp sequence at the 5'end of exon 31 (c.2446_2805del). Conclusions:Renal prognosis differs significantly for patients with small in-frame deletions versus large in-frame deletion splicing abnormalities. Determination of the pathogenicity and the splicing patterns of COL4A4 heterozygous splicing mutations using in vivo and in vitro transcriptional analysis may provide renal prognostic information.

Autosomal dominant osteopetrosis type Ⅱ: 2 cases report and literature review / 中华内分泌代谢杂志

Osteosclerosis is a rare hereditary bone metabolic disease, characterized by increased bone mass and density caused by bone resorption disorders, and any abnormal mutation involving osteoclast maturation or function will lead to the occurrence of osteopetrosis. Clinically, the prevalence of autosomal dominant osteopetrosis type Ⅱ(ADO-Ⅱ) is higher than that of other types of osteopetrosis, which involves multiple systems such as endocrine, bone, blood, nerve, ear-nose-throat, and oral cavity. Disease progression is insidious and easily overlooked, and there is no standard treatment. This article summarizes the clinical characteristics, examination data, diagnosis and treatment process of the two patients, analyzes multi-system symptoms, pathogenesis and treatment principles of the disease to improve the management of patients with ADO-Ⅱ.

Clinical technical operation specification of kidney transplantation for autosomal dominant polycystic kidney disease (2022 edition) / 器官移植

Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disease and one of the most common causes for end-stage renal disease (ESRD). Kidney transplantation is the optimal renal replacement therapy for ADPKD patients complicated with ESRD. Currently, scholars at home and abroad have a certain controversy about whether polycystic kidney resection is necessary in ADPKD patients before kidney transplantation, and the criteria and methods for polycystic nephrectomy also differ. To further standardize the clinical technical operation of kidney transplantation in ADPKD patients, experts in organ transplantation organized by Branch of Organ Transplantation of Chinese Medical Association formulated this specification from the aspects of diagnosis of ADPKD, indications and contraindications of kidney transplantation for ADPKD, preoperative evaluation and treatment, polycystic nephrectomy, and postoperative management, etc.

Combined liver-kidney transplant in polycystic diseases: a case report

ABSTRACT Polycystic liver disease, a hereditary pathology, usually manifests as autosomal dominant polycystic kidney disease. The many cysts in the liver cause massive hepatomegaly, majorly affecting the patient's quality of life. In cases of refractory symptoms, liver transplantation is the only treatment choice. A 43-year-old woman was followed up as a hepatology outpatient in August 2020, with a progressive increase in abdominal volume, lower limb edema, and cachexia. The patient was diagnosed with polycystic renal and liver disease with massive hepatomegaly in March 2021, a combined kidney-liver transplant. Liver size represented 13% of the patient's corporal composition, weighing 8.6kg. The patient was discharged on the 7th postoperative day with no complications. Only 10-20% of patients with polycystic liver disease have clinical manifestations, most of which result from hepatomegaly. An increase in liver volume deteriorates liver function until the condition becomes end-stage liver disease, as kidney function is already compromised; liver-kidney transplantation remains the only treatment choice. The case described drew significant attention to the massive hepatomegaly presented in the patient, with the liver representing over 10% of the patient's body weight, approximately five to six times larger than a normal-sized liver.

Autosomal dominant neurodevelopmental disorders associated with KIF1A gene variants in 6 pediatric patients / 浙江大学学报·医学版

OBJECTIVES@#To analyze the clinical and genetic characteristics of children with autosomal dominant neurodevelopmental disorders caused by kinesin family member 1A (KIF1A) gene variation.@*METHODS@#Clinical and genetic testing data of 6 children with KIF1A gene de novo heterozygous variation diagnosed in Shanghai Children's Medical Center Affiliated to Shanghai Jiao Tong University School of Medicine from the year 2018 to 2020 were retrospectively analyzed. Pathogenic variants were identified based on whole exome sequencing, and verified by Sanger sequencing. Moreover, the effect of variants on three-dimensional structure and stability of protein was analyzed by bioinformatics.@*RESULTS@#Among 6 patients there were 4 males and 2 females, and the age of consultation varied from 7 months to 18 years. All cases had varying degrees of motor developmental delay since childhood, and 4 of them had gait abnormalities or fell easily. In addition, 2 children were accompanied by delayed mental development, epilepsy and abnormal eye development. Genetic tests showed that all 6 cases had heterozygous de novo variations of KIF1A gene, including 4 missense mutations c.296C>T (p.T99M), c.761G>A (p.R254Q), c.326G>T (p.G109V), c.745C>G (p.L249V) and one splicing mutation c.798+1G>A, among which the last three variants have not been previously reported. Bioinformatics analysis showed that G109V and L249V may impair their interaction with the neighboring amino acid residues, thereby impacting protein function and reducing protein stability, and were assessed as "likely pathogenic". Meanwhile, c.798+1G>A may damage an alpha helix in the motor domain of the KIF1A protein, and was assessed as "likely pathogenic".@*CONCLUSIONS@#KIF1A-associated neurological diseases are clinically heterogeneous, with motor developmental delay and abnormal gait often being the most common clinical features. The clinical symptoms in T99M carriers are more severe, while those in R254Q carriers are relatively mild.

Poliquistosis renal autosómica dominante: ¿quiénes se benefician del tratamiento con tolvaptán?. Estado del arte / Autosomal dominant polycystic kidney disease. Who can benefit from tolvaptan therapy? State of the art / Doença renal policística autossômica dominante: quem se beneficia do tratamento com tolvaptano? Estado da arte

Resumen: La poliquistosis renal autosómica dominante es la enfermedad renal hereditaria más frecuente. Se caracteriza por la progresiva aparición de quistes renales que suelen conducir a la enfermedad renal crónica extrema en la edad adulta. La aprobación del uso de tolvaptán (antagonista del receptor V2 de la vasopresina) ha marcado un cambio significativo en el tratamiento de esta enfermedad. En los últimos años apareció evidencia que demuestra el beneficio en iniciar tratamiento con tolvaptán en pacientes que presentan una enfermedad con rápida evolución. Se realiza una revisión descriptiva de los principales estudios clínicos publicados en el periodo 2012-2022 y se sugiere un esquema de utilidad para seleccionar aquellos pacientes que pueden beneficiarse del inicio de tratamiento.

Abstract: Autosomal dominant polycystic kidney disease is the most common hereditary kidney disease. It is characterized by the progressive appearance of renal cysts that usually lead to extreme chronic kidney disease in adulthood. The approval of the use of tolvaptán (V2 vasopressin receptor antagonist) has meant a significant change in the treatment of this disease. In recent years, evidence has proved the benefits of initiating treatment with tolvaptán in patients with a rapidly evolving disease. A descriptive review of the main clinical studies published in 2012-2022 period is carried out and a useful scheme is suggested to select those patients who can benefit from the start of treatment.

Resumo: A doença renal policística autossômica dominante é a doença renal hereditária mais comum. Caracteriza-se pelo aparecimento progressivo de cistos renais que geralmente levam à doença renal crônica extrema na idade adulta. A aprovação do uso do tolvaptano (antagonista do receptor de vasopressina V2) marcou uma mudança significativa no tratamento dessa doença. Nos últimos anos, surgiram evidências que demonstram o benefício de iniciar o tratamento com tolvaptano em pacientes com doença de evolução rápida. Faz-se uma revisão descritiva dos principais estudos clínicos publicados no período 2012-2022 e sugere-se um esquema útil para selecionar aqueles pacientes que podem se beneficiar do início do tratamento.

Familial Primary Open Angle Glaucoma

Primary open-angle glaucoma (POAG), also known as chronic simple glaucoma, is usually an inherited disease. Inheritance is considered multifunctional and polygenic. Glaucoma is the second leading cause of irreversible blindness worldwide, of which POAG is the most common. First-degree relatives of POAG patients are at increased risk. A reasonable risk for siblings is four and twice the risk of the normal population for the offspring, although the number of surveys varies. This case series of eight family members with POAG illustrates the stealth nature of POAG and the devastating vision loss it can cause as it progresses; emphasizing regular and comprehensive eye examinations during its early stage.

NOS3 gene intron 4 a/b polymorphism is associated with ESRD in autosomal dominant polycystic kidney disease patients / O polimorfismo intron 4 a/b do gene NOS3 está associado à DRET em pacientes com doença renal policística autossômica dominante

Abstract Introduction: Endothelial nitric oxide synthase (eNOS) genes have been implicated in renal hemodynamics as potent regulators of vascular tone and blood pressure. It has been linked to a reduction in plasma nitric oxide levels. Several studies have recently been conducted to investigate the role of NOS3 gene polymorphisms and end-stage renal disease (ESRD). However, the results are still unclear and the mechanisms are not fully defined. As a result, we conducted a meta-analysis to examine the relationship between NOS3 gene polymorphism and ESRD in autosomal polycystic kidney disease (ADPKD) patients. Methods: To assess the relationship between NOS3 gene polymorphism and ESRD, relevant studies published between September 2002 and December 2020 were retrieved from the PubMed (Medline), EMBASE, Google Scholar, and Web of Science databases. The pooled odds ratio (OR) and 95 % confidence interval (CI) were calculated using a fixed-effect model. To assess the heterogeneity of studies, we used Cochrane's Q test and the Higgins and Thompson I2 statistics. Results: Our meta-analysis of 13 studies showed that the presence of the two NOS3 gene polymorphisms significantly increased ESRD risk in ADPKD patients with 4a/b gene polymorphism (aa+ab vs. bb: OR=1.95, 95% CI=1.24-3.09, p=0.004). In addition, no significant association was found between the NOS3 894G>T (Glu298Asp) polymorphism and the risk of ESRD in ADPKD patients (GT+TT vs. GG: OR=1.21, 95% CI=0.93-1.58, p=0.157). There was no evidence of publication bias. Conclusions: The findings of the current meta-analysis suggest that NOS3 intron 4a/b polymorphism plays a vital role in the increasing risk of ESRD in ADPKD patients.

Resumo Introdução: Genes da óxido nítrico sintase endotelial (eNOS) têm sido implicados na hemodinâmica renal como potentes reguladores do tônus vascular e pressão arterial. Tem sido vinculado a uma redução nos níveis plasmáticos de óxido nítrico. Realizou-se recentemente vários estudos para investigar o papel de polimorfismos do gene NOS3 e doença renal em estágio terminal (DRET). Entretanto, os resultados ainda não são claros e os mecanismos não estão totalmente definidos. Como resultado, realizamos meta-análise para examinar a relação entre polimorfismo do gene NOS3 e DRET em pacientes com doença renal policística autossômica dominante (DRPAD). Métodos: Para avaliar a relação entre polimorfismo do gene NOS3 e DRET, recuperou-se estudos relevantes publicados entre Setembro-2002 e Dezembro-2020 dos bancos de dados PubMed (Medline), EMBASE, Google Scholar, Web of Science. Calculamos odds ratio (OR) e intervalo de confiança (IC) de 95% utilizando modelo de efeitos fixos. Para avaliar a heterogeneidade dos estudos, utilizamos teste Q de Cochrane e estatísticas I2 de Higgins e Thompson. Resultados: Nossa meta-análise de 13 estudos mostrou que a presença dos dois polimorfismos do gene NOS3 aumentou significativamente o risco de DRET em pacientes com DRPAD com polimorfismo do gene 4a/b (aa+ab vs. bb: OR=1,95; IC 95%=1,24-3,09; p=0,004). Ademais, não encontramos associação significativa entre polimorfismo 894G>T NOS3 (Glu298Asp) e risco de DRET em pacientes com DRPAD (GT+TT vs. GG: OR=1,21; IC 95%=0,93-1,58; p=0,157). Não houve evidência de viés de publicação. Conclusões: Achados da meta-análise atual sugerem que o polimorfismo intron 4a/b do NOS3 desempenha papel vital no aumento do risco de DRET em pacientes com DRPAD.

Mental retardation autosomal dominant 35 caused by de novo missense variants in PPP2R5D gene: a case report and literature review / 中华神经科杂志

Objective:To enhance understanding of mental retardation autosomal dominant 35 (MRD35) by analyzing the clinical and genetic characteristics of the disease.Methods:Clinical and genetic data of 1 case of MRD35 in Beijing Children′s Hospital in July 2018 were reported, and literature review was conducted.Results:The male proband, 1 year and 3 months old, was admitted with the clinical manifestations including mental retardation, low-grade fever, a large forehead, flat nose, open mouth, and hypomyotonia. The brain magnetic resonance imaging showed enlarged lateral ventricles, cavum septum, cavum verge and cavum velum interpositum cyst. The whole exome sequencing test showed that the proband carried a missense mutation c.1258 G>A, (p.E420K) in the PPP2R5D gene, and the mutation was de novo confirmed by Sanger sequencing. There were ten literatures reported, including a total number of 31 cases. Counting on this case, totally 32 cases were included. Among the 32 patients, 32 cases (100.0%) had mental retardation, 26 cases (81.3%) with motor retardation, 26 cases (81.3%) with macrocephaly, 8 cases (25.0%) with epilepsy. Facial dysmorphic features, ocular abnormalities, skeletal abnormalities, and cardiac malformations were also reported. All reported individuals had missense mutations of PPP2R5D gene and were autosomal dominantly inherited. Conclusions:The main clinical manifestations of MRD35 include growth retardation/mental retardation, severe speech impairment, macrocephaly, hypomyotonia, seizures and dysmorphic facial features. A novel missense mutation in the PPP2R5D gene is the cause of MRD35.

Genotype and phenotype analysis of children with autosomal dominant inheritance Alport syndrome / 中华实用儿科临床杂志

Objective:To analyze the clinicopathological and gene mutation characteristics of children with autosomal dominant inheritance Alport syndrome (ADAS), and to improve the understanding of ADAS.Methods:Ten children with ADAS diagnosed in the Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology from September 2016 to February 2020 were enrolled.The clinicopathological and gene mutation features were retrospectively analyzed, and the patients were followed up.Results:(1) The median age at diagnosis was 5.7 (2.4, 9.8) years.Of 10 children, 6 cases (60.0%) showed a family history of renal failure, 4 cases (40.0%) presented with hematuria and proteinuria at diagnosis, and 2 cases (20.0%) suffered a high-frequency hearing loss.Renal biopsy showed extensive splitting and lamellation of the glomerular basement membrane (GBM) dense layer in 4 cases (40.0%), and segmental splitting and lamellation in 6 cases (60.0%). (2)Among 10 children, 4 cases (40.0%) were heterozygous mutations of COL4A3 gene, including 2 point mutations of glycine, and 2 splicing mutations.The other 6 cases (60.0%) were heterozygous mutations of COL4A4 gene, including collagen glycine point mutations in 4 cases, nonsense mutation in 1 case and large deletion in 1 case.Six mutations were new and never reported before. Conclusions:The early clinical presentations of children with ADAS are often atypical and extrarenal manifestations are less common.The GBM dense layer is mainly featured by segmental splitting and lamellation.Glycine point mutations account for the majority of the gene mutations.

Feasibility and perioperative safety of retroperitoneal laparoscopic nephrectomy for autosomal dominant polycystic kidney before kindey transplantation / 国际外科学杂志

Objective:To evaluate the feasibility and perioperative safety of retroperitoneal laparoscopic nephrectomy for autosomal dominant polycystic kidney disease (ADPKD) before kidney transplantation.Methods:A total of 22 patients with ADPKD who underwent laparoscopic polycystic nephrectomy before kidney transplantation in Beijing Friendship Hospital, Capital Medical University from January 2013 to December 2020 were enrolled in this retrospective study. Preoperative epidemiological data, operation time, intraoperative blood loss, perioperative blood transfusion, conversion rate, postoperative gastrointestinal function recovery time, drainage tube placement time, postoperative hospital stay, incidence and severity of complications were collected.Results:The mean age of all patients in this study was (50.95±9.28) years old, and the mean preoperative polycystic kidney diameter was (18.83±2.38) cm. In all patients, 20 patients were scheduled for polycystic nephrectomy due to transplantation and 2 patients were done for polycystic renal cyst rupture and hemorrhage. The mean operation time of all patients was (191.14±70.46) min, and the median intraoperative blood loss was 100 mL. Among them, 5 patients had large intraoperative blood loss, and were given intraoperative blood transfusion. Two of all patients were converted to open due to severe intraoperative adhesions. In terms of postoperative recovery, the mean recovery time of gastrointestinal function was (2.09±0.61) d, the mean time of abdominal drainage tube placement was (5.32±2.08) d, the mean postoperative hospital stay was (7.55±2.34) d. In terms of postoperative complications, 4 patients developed postoperative incision pain, bleeding or other complications, but all improved after symptomatic treatment.Conclusions:For patients with ADPKD, original polycystic kidney can be effectively resected by retroperitoneoscopy before transplantation. At the same time, the operation time is short, and patients have quick postoperative recovery, even the incidence and severity of postoperative complications are low. Therefore, retroperitoneal laparoscopic nephrectomy can be used as the first choice for the removal of original polycystic kidney before renal transplantation in ADPKD patients.

Influence of prophylactic resection of orthotopic polycystic kidney disease on perioperative complications and surgical difficulty of renal transplantation in patients with ADPKD / 国际外科学杂志

Objective:To explore whether prophylactic resection of orthotopic polycystic kidney before allogeneic kidney transplantation can reduce the incidence and severity of perioperative complications in patients with end-stage renal disease due to autosomal dominant polycystic kidney disease (ADPKD), and reduce the difficulty of surgery.Methods:A retrospective case-control study method was used to recruit a total of 27 patients who were diagnosed with ADPKD and underwent allogeneic kidney transplantation in Beijing Friendship Hospital, Capital Medical University from January 2013 to January 2021, they were divided into prophylactic resection group ( n=19) and non-prophylactic resection group ( n=8) according to whether orthotopic polycystic kidney disease was prophylactic resection before transplantation. Patients in prophylactic resection group underwent orthotopic polycystic kidney resection before transplantation, while patients in non-prophylactic resection group didn′t. The indexes such as hemoglobin, platelet, albumin, left ventricular wall thickness, left ventricular ejection fraction, difficulty of kidney transplantation, average postoperative hospital stay, pain, and complication rate before kidney transplantation were analyzed and compared between the two groups. Measurement data were expressed as mean ± standard deviation ( ± s), and independent sample t-test was used for comparison between groups; Chi-square test was used for comparison of enumeration data between groups. Results:There was no significant difference in the general status of hemoglobin, platelets, albumin, left ventricular wall thickness, and left ventricular ejection fraction between the two groups before kidney transplantation ( P>0.05). However, the polycystic kidney volume [(2 409.8±1 899.8) cm 3] in the prophylactic resection group was greater than that in the non-prophylactic resection group [(1 340.2±290.6) cm 3], and the difference was statistically significant ( P=0.027). In terms of postoperative complications, 9 patients in the prophylactic resection group and 5 patients in the non-prophylactic resection group developed long-term low back pain or hematuria after transplantation, which were considered to be related to the unresected polycystic kidney disease, but the difference was not statistically significant ( P=0.678). Meanwhile, in both two groups, 3 patients underwent orthotopic polycystic nephrectomy after transplantation due to severe polycystic kidney complications. Although the incidence of complications in the prophylactic resection group (15.8%) was lower than that in the non-prophylactic resection group (37.5%), the difference was not statistically significant ( P=0.319). Conclusion:Prophylactic resection of orthotopic polycystic kidney before kidney transplantation can reduce the incidence and severity of polycystic kidney-related complications after transplantation, but has little effect on the operation time and intraoperative blood loss of kidney transplantation.

Research progress on role of autophagy in ADPKD / 中国药理学通报

Autophagy is a process that delivers cytoplasmic components to lysosome for degradation, which plays an important role in intracellular homeostasis and achieving self-renewal.Recent studies have shown a close relation between autophagy and renal cystogenesis in ADPKD.Further studies show that there are two phenomena of autophagy impairment and autophagy enhancement in the ADPKD disease model.Autophagy disorders influence the occurrence and development of ADPKD.Therefore, the regulation of autophagy may be a new strategy for ADPKD treatment.Medicines that regulate autophagy through mTOR-dependent and mTOR-independent pathways also show a positive effect in alleviating ADPKD symptoms.This paper reviews the progress of the role of autophagy in ADPKD and provides reference for further research of autophagy in ADPKD and its medicine regulation.

Are Saunas Beneficial or Harmful for Autosomal Dominant Polycystic Kidney Disease? Examination with Model Mouse / 日本温泉気候物理医学会雑誌

  Background: Heat shock proteins (Hsps), expression of which are induced by thermal treatment, function in the protection of kidneys by suppressing apoptosis and maintaining renal tubular viability. Moreover, recently, it has been indicated that the expression of Hsps can be a therapeutic target for autosomal dominant polycystic kidney disease (ADPKD). We investigated the effect of dry sauna therapy on ADPKD model mice.  Methods and Results: The mice (male DBA/2FG-pcy mice) were categorized into three groups: controls, TS: pcy mice subjected to prolonged sauna with administered water containing 4% sucrose, SW: pcy mice administered water containing 4% sucrose. The TS group was subjected to sauna sessions twice a week for four weeks. The TS group attained and were maintained at rectal temperatures of approximately 39.0°C, until they were carefully removed from the far infrared-ray device. After 4 weeks of sauna treatment, creatinine and blood-urea-nitrogen (BUN) levels determined by an enzymatic method. The heat shock protein (HSP) or cell growth and size related proteins were analyzed by western blotting. The TS group exhibited marginally higher creatinine and BUN levels than did the control and SW groups, however, the differences were not significant. However, cyst enlargement in the TS group reduced significantly compared to that of the control group. HSP90 expression was slightly decreased in the TS and SW groups relative to the control group (p < 0.01 or p < 0.001, vs. control), as was Erk expression, which is linked to cyst development and proliferation (p < 0.05, TS vs. control). Hsp27 expression and phosphorylation level in the SW group were comparable with that of the control group. However, the TS group had increased levels of Hsp27 and phosphorylation (NS). The expression of pro-caspase-3 in the TS group was marginally lower than that in the control group. However, the activity of caspase-3 in all groups showed no differences.  Conclusion: The findings of this study indicated that 4 weeks of sauna treatment could cause transient dehydration and related renal dysfunction and led to the risk of stimulating cyst growth by increased Hsp27 expression. Moreover, we concluded that prevention of dehydration and cyst growth could be suppressed by taking an appropriate amount of water directly after sauna treatment.

Trastornos metabólicos urinarios en pacientes urolitiásicos con enfermedad renal poliquística y sin ella / Urinary metabolic disorders in urolithiasis patients with and without polycystic kidney disease

Introducción: La urolitiasis se ha incrementado en las últimas décadas. La enfermedad renal poliquística autosómica dominante (ERPAD), enfermedad renal hereditaria más frecuente, ocupa un lugar preponderante. Objetivos: Identificar la frecuencia de presentación de los trastornos metabólicos urinarios en pacientes litiásicos cubanos con ERPAD y sin ella Métodos: Estudio descriptivo, transversal. Fueron estudiados 579 pacientes adultos sin ERPAD, seleccionados por muestreo simple aleatorio y los 21 pacientes con ERPAD, del total de pacientes con litiasis urinaria que se realizó estudio metabólico renal en el Laboratorio de Fisiopatología Renal del Instituto de Nefrología, en el periodo 2010-2015. Los datos fueron tomados de la historia clínica y del informe de estudio metabólico renal. La información se procesó de forma automatizada (SPSS 22.0). Se utilizó el promedio, desviación estándar, análisis de distribución de frecuencias y el test de homogeneidad. Resultados: En los pacientes con ERPAD predominó el sexo femenino (57,1 por ciento), mientras que en los pacientes sin ERPAD, el masculino (63,4 por ciento). Los trastornos más frecuentes en la población no poliquística fueron hipercalciuria (45,3 por ciento) e hipofosfatemia (17,1 por ciento). En los poliquísticos, aclaramiento aumentado de ácido úrico (38,1 por ciento) e hipercalciuria (23,8 por ciento). Se encontraron diferencias estadísticamente significativas para aumento del aclaramiento de ácido úrico (p = 0,01) e hiperfosfatemia (p = 0,04). Conclusiones: Los principales trastornos metabólicos de los pacientes litiásicos, tanto poliquísticos como no poliquísticos, son el aclaramiento de ácido úrico aumentado, hipercalciuria, hiperuricosuria e hipofosfatemia, aunque el orden de presentación es diferente. El aclaramiento de ácido úrico aumentado y la hiperfosfatemia se presentan con mayor frecuencia en los pacientes litiásicos poliquísticos(AU)

Introduction: Urolithiasis has increased in recent decades. Autosomal dominant polycystic kidney disease (ADPKD), the most common of all hereditary kidney diseases, occupies a predominant position in terms of incidence. Objectives: Identify the frequency of occurrence of urinary metabolic disorders in Cuban urolithiasis patients with and without ADPKD. Methods: A descriptive cross-sectional study was conducted of 579 adult patients without ADPKD selected by simple random sampling, and 21 patients with ADPKD, from the total urolithiasis patients undergoing renal metabolic evaluation at the Renal Physiopathology Laboratory of the Institute of Nephrology in the period 2010-2015. Data were obtained from medical records and reports of renal metabolic studies. Information was processed with the statistical software SPSS version 22.0. Average and standard deviation were estimated and use was made of frequency distribution analysis and homogeneity testing. Results: A predominance was found of female sex among patients with ADPKD (57.1 percent) and male sex among patients without ADPKD (63.4 percent). The most common disorders were hypercalciuria (45.3 percent) and hypophosphatemia (17.1 percent) in the non-polycystic population, and increased uric acid clearance (38.1 percent) and hypercalciuria (23.8 percent) in polycystic patients. Statistically significant differences were found in uric acid clearance increase (p = 0.01) and hyperphosphatemia (p = 0.04). Conclusions: The main metabolic disorders of lithiasis patients, polycystic as well as non-polycystic, are increased uric acid clearance, hypercalciuria, hyperuricosuria and hypophosphatemia, with a varying order of presentation. Increased uric acid clearance and hyperphosphatemia are more common in polycystic lithiasis patients(AU)

Treacher Collins Syndrome: A Rare and Special Case Report of a 9-Year-Old Boy from Saudi Arabia

Treacher Collins syndrome (TCS) is characterized by downslanting palpebral fissures on both sides, malar hypoplasia, micrognathia, and external ear abnormalities. Hypoplasia of the zygomatic bones and jaw may make it difficult to eat and breathe. TCS, also known as Franceschetti syndrome or mandibulofacial dysostosis, is an autosomal dominant craniofacial condition with a wide range of symptoms. Edward Treacher Collins (1862?1932), an English ophthalmologist, first defined the syndrome’s fundamental characteristics in 1900. This syndrome is approximately affecting 1 in 50,000 live births with equal gender affection. In Saudi Arabia, it follows a similar pattern of prevalence. Antimongoloid slanting palpebral fissures, colobomas of the lower eyelid, hypoplasia of the zygoma and mandible, auditory microtia, conductive hearing loss, obstructive sleep apnea, and a range of orofacial abnormalities are the most prevalent clinical symptoms of TCS. In this case report, the author describes a deep-rooted analysis of the clinical features of TCS in a 9-year-old boy as well as his follow-up case. The study was conducted for a period of 9 years from birth to 9 year-old age, which makes this case report as a special rare 9-year follow-up case report from Saudi Arabia.

Characteristics of autosomal dominant retinal diseases and gene therapy strategies / 中华实验眼科杂志

Inherited retinal diseases (IRDs), one type of the major eye diseases resulting in blindness, can be caused by more than 270 identified causative genes.The most common form of IRDs is retinitis pigmentosa.There is no generally accepted cure for vision impairment due to IRDs.In recent years, the first gene replacement therapy has been approved for the treatment of autosomal recessive IRDs.Because of the variety of pathogenesis, including gain-of-function and dominant-negative effects in addition to a few loss-of-function mutations, gene replacement therapy of autosomal dominant IRDs is not always effective.The clinical manifestations of autosomal dominant IRDs are extremely complex, and there is no appropriate treatment in clinical practice.The latest progresses in pathogenesis, clinical features, treatment strategies and directions of autosomal dominant IRDs globally were reviewed, and the most common genes causing autosomal dominant IRDs were summarized in this article in order to provide a deeper understanding of autosomal dominant IRDs.