浙江大学医学院：肾脏疾病遗传学（PPT讲稿）Genetics of Renal Disorders

Genetics of renal disorders 张成宁 zhangxianning@zju.edu.cn Tel:13105819271;88208367 Office: C303, Teaching building 2016/04

Genetics of Renal Disorders 张咸宁 zhangxianning@zju.edu.cn Tel：13105819271; 88208367 Office: C303, Teaching Building 2016/04

Learning obiectives 了解泌尿系统疾病的遗传学研究现状 掌握相关的疾病基因组学研究技术新进 展

Learning Objectives • 了解泌尿系统疾病的遗传学研究现状。 • 掌握相关的疾病基因组学研究技术新进 展

Autosomal dominant polycystic kidney disease Thompson &thompson genetics in Medicine gn ed 2016. pp 113 302: Clinical Case Studies: 37 Polycystic Kidney disease Recommended reading: QiX-P,., Zhang X-n*. genetic diagnosis of autosomal dominant polycystic kidney disease by targeted capture and next-generation sequencing: utility and limitations. Gene, 201315l6(1):93-100

Autosomal dominant polycystic kidney disease Thompson &Thompson Genetics in Medicine, 8 th ed. 2016. pp 113、302；Clinical Case Studies: 37. Polycystic Kidney Disease Recommended Reading: Qi X-P, …, Zhang X-N*. Genetic diagnosis of autosomal dominant polycystic kidney disease by targeted capture and next-generation sequencing: utility and limitations. Gene, 2013;516(1):93-100

Recommended Reading Gawad C, Koh w, Quake sr single-cell genome sequencing: current state of the science. Nat rey genet 2016;17(3):175-188

Recommended Reading Gawad C, Koh W, Quake SR. Single-cell genome sequencing: current state of the science. Nat Rev Genet. 2016;17(3):175-188

Renal disorders Get Fn Access and More Expertconsult.com 先天性肾及淞尿道异常 EMERY AND RIMOIN'S 62 Congenital Anomalies of the Kidney and Urinary Tract, 241 ESSENTIAL MEDICAL GENETICS 6332性疾病 Angela Sun, Raymond Y Wang, and Dechu P Puliyanda 64 Nephrotic Disorde251病变疾病 658teoy小管疾病 Richard E Hilman DAVID L RIMOIN REED E PYERITZ 66 Cancer of the Kidney and Urogenital Tract, 259 BRUCE R KORF m0mG肾及泌尿生殖道癌症

Introduction Kidney diseases pose a significant global disease burden The most common form, chronic kidney disease(ckd) affects an estimated 10% of adults in many countries and the prevalence IS Increasing Over 250 syndromes and monogenic disorders have been reported to have an increased risk for congenital anomalies of the kidney and urinary tract (caKut)

Introduction • Kidney diseases pose a significant global disease burden • The most common form, chronic kidney disease (CKD), affects an estimated 10% of adults in many countries and the prevalence is increasing • Over 250 syndromes and monogenic disorders have been reported to have an increased risk for congenital anomalies of the kidney and urinary tract (CAKUT)

TABLE 62-4 DIsorders Assoclated wIth Renal Dysplasla Disorder Major Features Renal anomaly Etiology Genes Asplenia with Bilateral right or left embryonic Renal dysplasia AR②208530 cardiovascular primordia, asplenia anomalies polysplenia, complex heart Bardet-Biedl Mental retardation, pigmentary Renal dysplasia, cystic tubular AR (209900) BB51-15 retinopathy, polydactyly, disease, focal segmental obesity, hypogenitalism glomerulosclerosis, bladder det stabllity Beckwith-Wiedemann Omphalocele, macroglossia, Nephromegaly, renal medullary AD (130650) CDKN1C organomegaly, islet cell dysplasia, Wilms tumor, imprinting error hyperplasia, adrenal nephrocalcinosis uniparental disomy cytomegaly, embryonic duplication, inver tumors. macrosomia sion or translocation of 11p15.5 Branchio-oto-renal Mixed hearing loss, Mondini Renal dysplasia, agenesis, and AD (113650) EYAl cochlear malformations copy: ureteral anomalies pinnae anomalies, branchial S/X5 cleft fistulas, preauricular pits Caudal dysplasia Sacral agenesis/hypoplasia, Renal dysplasia and agenesis; Heterogeneous, lower limb and skeletal anomalies of urethra and maternal anomalies. anal atresia bladder diabetes in anomalies of the uterus some patients Cerebro-renal-digital Digital and limb anomalies, Renal dysplasia, ectopy. Heterogeneous brain malformations, other agenesis, ureteral anomalies anomalies See Table 62-6 CHARGE syndrome Coloboma, heart anomalies, Cystic renal dysplasia, renal CHDZ choanal atresia. mental agenesis, ureteric anomalies AD(214800)

Chromosome See table 62-2 abnormalities Cloacal exstrophy Persistent cloaca, exstrophy Duplication of urethra; urethral Heterogeneous of cloaca. failure of fusion and ureteral anomalies of genital tubercles exstrophy of the bladder: omphalocele, vertebral renal dysplasia, agenesis, anomalies, spina bifida and ectopy cystica, abnormal genital structures Comelia de lange Microcephaly, in utero growth Renal dysplasia, agenesis, AD(122470) NIPBL retardation distinct facies hypopla micromelia, oligodactyly heart and other anomalies mental retardation Craniosynostosis Craniosynostosis(coronal), Segmental renal dysplasia, AR(218650) mental retardation- hypertelorism, choroidal cystic dysplasia clefting syndrome coloboma, mild meso melic shortening of limbs developmental delay seizures Cystic hamartoma of Hamartomatous pulmonary Medullary dysplasia, cellular Unknown lung and kidney cysts mesoblastic nephroma Denys-Drash syndrome Male pseudohermaphroditism, Diffuse mesangial sclerosis AD(194080) ambiguous genitalia, glomerulopathy, nephro- gonadal dysgenesis, gonado- blastoma(Wilms tumor) blastoma nephrotic syndrome, Toca segmental glomerulosclerosis

192 Chin Med J2013: 126(1) A 4 G c M Figure 1. Characteristic features of the CdlS patient and sequencing of the NIPBL gene. A: Arch-like confluent eyebrows, long thick eyelashes, anteverted nares, collapsed nasal bridge, downtuned comers of the mouth, thin lips and low-set ears. B: Upper-limb abnomalities. C: Chromographs of the partial CDNA sequence of NPBL from the patient (upper)and a healthy individual (lower) showing a heterozygous 4-base deletion in exon 44(. 7423 7426delGACA)(black arrow) Xu W-Z,., Zhang X-n". A novel de novo mutation of the nipbl gene in an isolated Chinese patient with Cornelia de lange syndrome. Chinese medical Journa,2013;126(1):191-192

Xu W-Z, ..., Zhang X-N*. A novel de novo mutation of the NIPBL gene in an isolated Chinese patient with Cornelia de Lange syndrome. Chinese Medical Journal, 2013;126(1):191-192

Disorder Major features Renal anomaly Etiology Genes Digeorge syndrome Sacral meningocele, Unilateral renal agenesis, AD (188400) 22q11. 2 deletion hydrocephalus, conotrun. dysplasia, hydronephrosis cal heart anomalies hypoplasia of the thymus and parathyroid glands, hypocalcemia Early amnion rupture Digital and limb amputations Renal dysplasia, agenesis, and Sporadic ring constrictions, facial ectopy, ureteric anomalies clefts, body wall defects brain anomalies Ectrodactyly Renal agenesis or cystic AD (129900) ectodermal dysplasia, clef lip/pa dysplasia, ureteral and fEC dysplasia-clefting abnormal hearing, internal bladder anomalies, TP63 (EEC) genital tract anomalies, anal duplicated collecting system atresia Fanconi pancytopenia Pancytopenia, anemia; Renal agenesis (39%)or AR (227650) FANC(A, G-G L 4L-P) radial aplasia dysplasia, duplication of hypoplasia, microcephaly, pelvis and/or ureter, ectopic short stature variable eye, or horseshoe kidney. ea, and heart anomalies hydronephrosis increased chromosome breakage