EU Research on Rare Diseases https://ec.europa.eu/info/research-and-innovation/research-area/health-research-and-innovation/rare-diseases_en [Accessed 12 October 2020].

Rare Diseases at FDA https://www.fda.gov/patients/rare-diseases-fda [Accessed 12 October 2020] .

Harambat J. van Stralen K.J. Kim J.J. Tizard E.J.

Epidemiology of chronic kidney disease in children.

Pediatr Nephrol. 27: 363-373

Kidney Disease Statistics for the United States https://www.niddk.nih.gov/health-information/health-statistics/kidney-disease [Accessed 12 October 2020] .

What do we know about chronic renal failure in young adults?.

Pediatr Nephrol. 24: 1913-1919Queißer-Luft A. Stolz G. Wiesel A. Schlaefer K. Spranger J.

Malformations in newborn: results based on 30940 infants and fetuses from the Mainz congenital birth defect monitoring system (1990-1998).

Arch Gynecol Obstet. 266: 163-167Adalat S. Bockenhauer D. Ledermann S.E. Hennekam R.C. Woolf A.S.

Renal malformations associated with mutations of developmental genes: messages from the clinic.

Pediatr Nephrol. 25: 2247-2255Clissold R.L. Hamilton A.J. Hattersley A.T. Ellard S. Bingham C.

HNF1B-associated renal and extra-renal disease.

Nat Rev Nephrol. 11: 102-112Adalat S. Hayes W. Bryant W. Booth J. Woolf A.S. Kleta R. Subtil S. Colclough K. Ellard S. Bockenhauer D.

HNF1B mutations are associated with a Gitelman-like tubulopathy that develops during childhood.

Kidney Int Rep. 4: 1304-1311Woolf A.S. Lopes F.M. Ranjzad P. Roberts N.A.

Congenital disorders of the human urinary tract: recent insights from genetic and molecular studies.

Front Pediatr. 7: 136Jenkins D. Bitner-Glindzicz M. Malcolm S. Allison J. Hu C.C. Winyard P.J. et al.

De novo Uroplakin IIIa mutations cause renal adysplasia leading to severe kidney failure.

J Am Soc Nephrol. 16: 2141-2149Schönfelder E.M. Knüppel T. Tasic V. Miljkovic P. Konrad M. Wühl E. Antignac C. Bakkaloglu A. Schaefer F. Weber S. ESCAPE Trial Group

Mutations in Uroplakin IIIA are a rare cause of renal hypodysplasia in humans.

Am J Kidney Dis. 47: 1004-1012Jenkins D. Bitner-Glindzicz M. Malcolm S. Allison J. de Bruyn R. Thomas D.F.M. Belk R.A. Feather S.A. Bingham C. Southgate J. Woolf A.S.

Mutation analyses of Uroplakin II in children with renal tract malformations.

Nephrol Dial Transplant. 21: 3415-3421Houweling A.C. Beaman G.M. Postma A.V. Gainous T.B. Lichtenbelt K.D. Brancati F. et al.

Loss-of-function variants in myocardin cause congenital megabladder in humans and mice.

J Clin Invest. 129: 5374-5380Farrugia M.K. Long D.A. Godley M.L. Peebles D.M. Fry C.H. Cuckow P.M. et al.

Experimental short-term fetal bladder outflow obstruction. I. Morphology and cell biology associated with urinary flow impairment.

J Pediatr Urol. 2: 243-253Caubit X. Gubellini P. Andrieux J. Roubertoux P. Metwaly M. Jacq B. et al.

TSHZ3 deletion causes an autism syndrome and defects in cortical projection neurons.

Nature Genet. 48: 1359-1369Caubit X. Lye C.M. Martin E. Core N. Long D.A. Vola C. et al.

Teashirt 3 is necessary for ureteral smooth muscle differentiation downstream of SHH and BMP4.

Development. 135: 3301-3310Jenkins D. Caubit X. Dimovski A. Matevska N. Lye C.M. Cabuk F. et al.

Analysis of TSHZ2 and TSHZ3 genes in congenital pelvi-ureteric junction obstruction.

Nephrol Dial Transplant. 25: 54-60Weber S. Thiele H. Mir S. Toliat M.R. Sozeri B. Reutter H. et al.

Muscarinic acetylcholine receptor M3 mutation causes urinary bladder disease and a prune-belly-like syndrome.

Am J Hum Genet. 89: 668-674Beaman G.M. Galatà G. Teik K.W. Urquhart J.E. Aishah A. O’Sullivan J. et al.

A homozygous missense variant in CHRM3 associated with familial urinary bladder disease.

Clin Genet. 96: 515-520

Newman WG, Woolf AS. Urofacial Syndrome. 2013 Aug 22 [Updated 2018 Jun 7]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2018.

Stuart H.M. Roberts N.A. Bergu B. Daly S.B. Urquhart J.E. Bhaskar S. et al.

LRIG2 mutations cause urofacial syndrome.

Am J Hum Genet. 92: 259-264Kolvenbach C.M. Dworschak G.C. Frese S. Japp A.S. Schuster P. Wenzlitschke N. et al.

Rare variants in BNC2 are implicated in autosomal dominant congenital lower urinary tract obstruction.

Am J Hum Genet. 104: 994-1006Iqbal N.S. Jascur T.A. Harrison S.M. Edwards A.B. Smith L.T. Choi E.S. et al.

Prune belly syndrome in surviving males can be caused by hemizygous missense mutations in the X-linked filamin A gene.

BMC Med Genet. 21: 38Rieke J.M. Zhang R. Braun D. Yilmaz Ö. Japp A.S. Lopes F.M. et al.

SLC20A1 is involved in urinary tract and urorectal development.

Front Cell Dev Biol. 8: 567Harkness J.R. Beaman G.M. Teik K.W. Sidhu S. Sayer J.A. Cordell H.J. et al.

Early B-cell factor 3-related genetic disease mimics urofacial syndrome.

Kidney Int Rep. 5: 1823-1827Pratt M. Garritty C. Thuku M. Esmaeilisaraji L. Hamel C. Hartley T. et al.

Application of exome sequencing for prenatal diagnosis: a rapid scoping review.

Genet Med. 22: 1925-1934Darlow J.M. Darlay R. Dobson M.G. Stewart A. Gullett A.M. Charoen P. et al.

Genome-wide linkage and association study implicates the 10q26 region as a major genetic contributor to primary nonsyndromic vesicoureteric reflux.

Sci Rep. 7: 14595Lye C.M. Fasano L. Woolf A.S.

Ureter myogenesis: putting Teashirt into context.

J Am Soc Nephrol. 21: 24-30Roberts N.A. Hilton E.N. Lopes F.M. Randles M.J. Singh S. Gardiner N.J. et al.

Lrig2 and Hpse2, mutated in urofacial syndrome, pattern nerves in the urinary bladder.

Kidney Int. 95: 1138-1152Hu P. Deng F.M. Liang F.X. Hu C.M. Auerbach A.B. Shapiro E. et al.

Ablation of uroplakin III gene results in small urothelial plaques, urothelial leakage, and vesicoureteral reflux.

J Cell Biol. 151: 961-972Kong X.T. Deng F.M. Hu P. Liang F.X. Zhou G. Auerbach A.B. et al.

Roles of uroplakins in plaque formation, umbrella cell enlargement, and urinary tract diseases.

J Cell Biol. 167: 1195-1204Zhou H. Liu Y. He F. Mo L. Sun T.T. Wu X.R.

Temporally and spatially controllable gene expression and knockout in mouse urothelium.

Am J Physiol Renal Physiol. 299: F387-F395DeSouza K.R. Saha M. Carpenter A.R. Scott M. McHugh K.M.

Analysis of the sonic hedgehog signaling pathway in normal and abnormal bladder development.

PLoS One. 8e53675Carpenter A.R. Becknell B. Hirselj D.A. McHugh K.M.

Urinary diversion via cutaneous vesicostomy in the megabladder mouse.

Methods Mol Biol. 886: 393-402Singh S. Robinson M. Nahi F. Coley B. Robinson M.L. Bates C.M. et al.

Identification of a unique transgenic mouse line that develops megabladder, obstructive uropathy, and renal dysfunction.

J Am Soc Nephrol. 18: 461-471Matsui M. Motomura D. Karasawa H. Fujikawa T. Jiang J. Komiya Y. et al.

Multiple functional defects in peripheral autonomic organs in mice lacking muscarinic acetylcholine receptor gene for the M3 subtype.

Proc Natl Acad Sci USA. 97: 9579-9584Igawa Y. Zhang X. Nishizawa O. Umeda M. Iwata A. Taketo M.M. et al.

Cystometric findings in mice lacking muscarinic M2 or M3 receptors.

J Urol. 172: 2460-2464Stuart H.M. Roberts N.A. Hilton E.N. McKenzie E.A. Daly S.B. Hadfield K.D. et al.

Urinary tract effects of HPSE2 mutations.

J Am Soc Nephrol. 26: 797-804Manak I. Gurney A.M. McCloskey K.D. Woolf A.S. Roberts N.A.

Dysfunctional bladder neurophysiology in urofacial syndrome Hpse2 mutant mice.

Neurourol Urodyn. 39: 1930-1938Woolf A.S. Bosch R.J. Fine L.G.

Gene transfer into the mammalian kidney: micro-transplantation of retrovirus-transduced metanephric tissue.

Exp Nephrol. 1: 41-48Bosch R.J. Woolf A.S. Fine L.G.

Gene transfer into the mammalian kidney: direct retrovirus transduction of regenerating tubular epithelial cells.

Exp Nephrol. 1: 49-54

Gene therapy.

N Engl J Med. 381: 455-464Mendell J.R. Al-Zaidy S. Shell R. Arnold W.D. Rodino-Klapac L.R. Prior T.W. et al.

Single-dose gene-replacement therapy for spinal muscular atrophy.

N Engl J Med. 377: 1713-1722Nathwani A.C. Reiss U.M. Tuddenham E.G. Rosales C. Chowdary P. McIntosh J. et al.

Long-term safety and efficacy of factor IX gene therapy in hemophilia B.

N Engl J Med. 371: 1994-2004

Moving forward after two deaths in a gene therapy trial of myotubular myopathy.

Hum Gene Ther. 31: 695-696Markmann S. De B.P. Reid J. Jose C.L. Rosenberg J.B. Leopold P.L. et al.

Biology of the adrenal gland cortex obviates effective use of adeno-associated virus vectors to treat hereditary adrenal disorders.

Hum Gene Ther. 29: 403e12Nguyen G.N. Everett J.K. Kafle S. Roche A.M. Raymond H.E. Leiby J. et al.

A long-term study of AAV gene therapy in dogs with hemophilia A identifies clonal expansions of transduced liver cells.

Nat Biotechnol. 39: 47-55Foust K.D. Nurre E. Montgomery C.L. Hernandez A. Chan C.M. Kaspar B.K.

Intravascular AAV9 preferentially targets neonatal neurons and adult astrocytes.

Nat Biotechnol. 27: 59-65Foust K.D. Wang X. McGovern V.L. Braun L. Bevan A.K. Haidet A.M. et al.

Rescue of the spinal muscular atrophy phenotype in a mouse model by early postnatal delivery of SMN.

Nat Biotechnol. 28: 271-274Buckinx R. Van Remoortel S. Gijsbers R. Waddington S.N. Timmermans J.P.

Proof-of-concept: neonatal intravenous injection of AAV vectors results in successful transduction of myenteric and submucosal neurons in the mouse small and large intestine.

Neurogastroenterol Motil. 28: 299-305Massaro G. Mattar C.N.Z. Wong A.M.S. Sirka E. Buckley S.M.K. Herbert B.R. et al.

Fetal gene therapy for neurodegenerative disease of infants.

Nat Med. 24: 1317-1323Baruteau J.A. Perocheau D.P. Hanley J. Lorvellec M. Rocha-Ferreira E. Karda R. et al.

Argininosuccinic aciduria fosters neuronal nitrosative stress reversed by Asl gene transfer.

Nat Commun. 9: 3505Bey K. Ciron C. Dubreil L. Deniaud J. Ledevin M. Cristini J. et al.

Efficient CNS targeting in adult mice by intrathecal infusion of single-stranded AAV9-GFP for gene therapy of neurological disorders.

Gene Ther. 24: 325-332Picconi J.L. Muff-Luett M.A. Wu D. Bunchman E. Schaefer F. Brophy P.D.

Kidney-specific expression of GFP by in-utero delivery of pseudotyped adeno-associated virus 9.

Mol Ther Methods Clin Dev. 1: 14014Almeida-Porada G. Waddington S.N. Chan J.K.Y. Peranteau W.H. MacKenzie T. Porada C.D.

In utero gene therapy consensus statement from the IFeTIS.

Mol Ther. 27: 705-707Cao K.X. Booth A. Ourselin S. David A.L. Ashcroft R.

The legal frameworks that govern fetal surgery in the United Kingdom, European Union, and the United States.

Prenat Diagn. 38: 475-481Sheppard M. Spencer R.N. Ashcroft R. David A.L. EVERREST Consortium

Ethics and social acceptability of a proposed clinical trial using maternal gene therapy to treat severe early-onset fetal growth restriction.

Ultrasound Obstet Gynecol. 47: 484-4891Schneider H. Faschingbauer F. Schuepbach-Mallepell S. Körber I. Wohlfart S. Dick A. et al.

Prenatal correction of X-linked hypohidrotic ectodermal dysplasia.

N Engl J Med. 378: 1604-1610Rahim A.A. Wong A.M. Hoefer K. Buckley S.M. Mattar C.N. Cheng S.H. et al.

Intravenous administration of AAV2/9 to the fetal and neonatal mouse leads to differential targeting of CNS cell types and extensive transduction of the nervous system.

FASEB J. 25: 3505-3518Mattar C.N. Wong A.M. Hoefer K. Alonso-Ferrero M.E. Buckley S.M. Howe S.J. et al.

Systemic gene delivery following intravenous administration of AAV9 to fetal and neonatal mice and late-gestation nonhuman primates.

FASEB J. 29: 3876-3888Marquez L.L. Yuen E.C. McCray Jr., P.B.

Lentiviral vectors for the treatment and prevention of cystic fibrosis lung disease.

Genes (Basel). 10: 218Ahmed S.G. Waddington S.N. Boza-Morán M.G. Yáñez-Muñoz R.J.

High-efficiency transduction of spinal cord motor neurons by intrauterine delivery of integration-deficient lentiviral vectors.

J Control Release. 273: 99-107Shangaris P. Loukogeorgakis S.P. Subramaniam S. Flouri C. Jackson L.H. Wang W. et al.

In utero gene therapy (IUGT) using GLOBE lentiviral vector phenotypically corrects the heterozygous mumanised mouse model and its progress can be monitored using MRI techniques.

Sci Rep. 9: 11592

Gene therapy research for kidney disease.

Physiol Genomics. 51: 449-461Thiruchelvam N. Nyirady P. Peebles D.M. Fry C.H. Cuckow P.M. Woolf A.S.

Urinary outflow obstruction increases apoptosis and degregulates Bcl-2 and Bax expression in the fetal ovine bladder.

Am J Pathol. 162: 1271-1282Morris R.K. Malin G.L. Quinlan-Jones E. Middleton L.J. Hemming K. Burke D. et al.

Percutaneous vesicoamniotic shunting versus conservative management for fetal lower urinary tract obstruction (PLUTO): a randomised trial.

Lancet. 382: 1496-1506

Healthcare resource consumption for intermittent urinary catheterisation.

BMJ Open. 7e012360

Karet Frankl FE, Coward RJ, Gallagher H, Hilton R, Loud F, Modi K, Ormandy P, Woolf AS. UK Renal Research Strategy. UK Kidney Research Consortium. 2016;1-37.

Yamashita M. Rosser C.J. Zhou J.H. Zhang X.Q. Connor R.J. Engler H. et al.

Syn3 provides high levels of intravesical adenoviral-mediated gene transfer for gene therapy of genetically altered urothelium and superficial bladder cancer.

Cancer Gene Ther. 9: 687-691Rovner E. Chai T.C. Jacobs S. Christ G. Andersson K.E. Efros M. et al.

Evaluating the safety and potential activity of URO-902 (hMaxi-K) gene transfer by intravesical instillation or direct injection into the bladder wall in female participants with idiopathic (non-neurogenic) overactive bladder syndrome and detrusor overactivity from two double-blind, imbalanced, placebo-controlled randomized phase 1 trials.

Neurourol Urodyn. 39: 744-753

Cell and gene therapy clinical trials (catapult.org.uk) https://ct.catapult.org.uk/clinical-trials-database [Accessed 20 May 2021] .

https://pharmaphorum.com/news/novartis-reimbursement-options-as-eu-approves-ultra-pricey-sma-drug/#:∼:text=But%20Zolgensma%20is%20also%20the,costs%20further%20down%20the%20line. [Accessed 27 January 2021].

https://www.technologyreview.com/2017/04/21/152385/the-worlds-most-expensive-medicine-is-being-pulled-from-the-market/#:∼:text=The%20drug%2C%20Glybera%2C%20was%20the,deficiency%2C%20a%20rare%20metabolic%20disease. [Accessed 27 January 2021].

Next-generation AAV vectors-do not judge a virus (only) by its cover.

Hum Mol Genet. 28: R3-R14Shirley J.L. de Jong Y.P. Terhorst C. Herzog R.W.

Immune responses to viral gene therapy vectors.

Mol Ther. 28: 709-722