Advances and unmet needs in genetic, basic and clinical science in Alport syndrome: report from the 2015 International Workshop on Alport Syndrome

被引：44

作者：

Gross, Oliver ^{[1
]}

Kashtan, Clifford E. ^{[2
]}

Rheault, Michelle N. ^{[2
]}

Flinter, Frances ^{[3
]}

Savige, Judith ^{[4
]}

Miner, Jeffrey H. ^{[5
]}

Torra, Roser ^{[6
,7
]}

Ars, Elisabet ^{[6
,7
]}

Deltas, Constantinos ^{[8
]}

Savva, Isavella ^{[8
]}

Perin, Laura ^{[9
]}

Renieri, Alessandra ^{[10
,11
]}

Ariani, Francesca ^{[10
,11
]}

Mari, Francesca ^{[10
,11
]}

Baigent, Colin ^{[12
,13
]}

Judge, Parminder ^{[12
,13
]}

Knebelman, Bertrand ^{[14
,15
]}

Heidet, Laurence ^{[16
]}

Lagas, Sharon ^{[17
]}

Blatt, Dave ^{[18
]}

Ding, Jie ^{[19
]}

Zhang, Yanqin ^{[19
]}

Gale, Daniel P. ^{[20
]}

Prunotto, Marco ^{[21
]}

Xue, Yong ^{[22
]}

Schachter, Asher D. ^{[23
]}

Morton, Lori C. G. ^{[24
]}

Blem, Jacqui ^{[25
]}

Huang, Michael ^{[25
]}

Liu, Shiguang ^{[26
]}

Vallee, Sebastien ^{[27
]}

Renault, Daniel ^{[28
,29
]}

Schifter, Julia ^{[30
]}

Skelding, Jules ^{[31
]}

Gear, Susie ^{[31
]}

Friede, Tim ^{[32
]}

Turner, A. Neil ^{[33
]}

Lennon, Rachel ^{[34
]}

机构：

[1] Univ Med Goettingen, Clin Nephrol & Rheumatol, Gottingen, Germany

[2] Univ Minnesota, Sch Med, Dept Pediat, Minneapolis, MN 55455 USA

[3] Guys & St Thomas NHS Fdn Trust, Dept Clin Genet, London, England

[4] Univ Melbourne, Melbourne Hlth, Parkville, Vic, Australia

[5] Washington Univ, Sch Med, Div Nephrol, St Louis, MO USA

[6] Univ Autonoma Barcelona, Inherited Kidney Dis, Dept Nephrol, Fundacio Puigvert,IIB St Pau, Barcelona, Spain

[7] REDINREN, Barcelona, Spain

[8] Univ Cyprus, Dept Biol Sci, Mol Med Res Ctr, Nicosia, Cyprus

[9] Univ Southern Calif, Childrens Hosp Los Angeles, Los Angeles, CA USA

[10] Univ Siena, Med Genet Unit, Siena, Italy

[11] Azienda Osped Univ Senese, Genet Med, Siena, Italy

[12] Univ Oxford, Clin Trial Serv Unit, Nuffield Dept Populat Hlth, Oxford, England

[13] Univ Oxford, Epidemiol Studies Unit, Nuffield Dept Populat Hlth, Oxford, England

[14] Hop Necker Enfants Malad, AP HP, Div Nephrol, Paris, France

[15] Univ Paris 05, Paris, France

[16] Hop Necker Enfants Malad, Ctr Reference Malad Renales Hereditaires Enfant &, Serv Nephrol Pediat, Clin Maurice Lamy, Paris, France

[17] Alport Syndrome Fdn, Phoenix, AZ USA

[18] Alport Fdn Australia, Valentine, NSW, Australia

[19] Peking Univ, Hosp 1, Pediat Dept, Beijing, Peoples R China

[20] UCL, Ctr Nephrol, London, England

[21] F Hoffmann La Roche Ltd, Roche Pharma Res & Early Dev, Roche Innovat Ctr Basel, Basel, Switzerland

[22] Sanofi Genzyme, Global Clin Dev, Rare Dis Grp Therapeut Area, Naarden, Netherlands

[23] Novartis Inst BioMed Res, Translat Med, New Indicat Discovery Unit, Cambridge, MA USA

[24] Regeneron Pharmaceut, Fibrosis Res, Cardiovasc Res, Tarrytown, NY USA

[25] Regulus Therapeut, Clin Dev, San Diego, CA USA

[26] Sanofi Genzyme R&D Ctr, Dept Rare Dis, Framingham, MA USA

[27] Shire, Discovery Biol, Lexington, MA USA

[28] Assoc Informat & Res Genet Renal Dis AIRG, Paris, France

[29] FEDERG, Federat European Associat Patients Affected Genet, Brussels, Belgium

[30] Alport Israel, Haifa, Israel

[31] Alport UK, Tetbury, England

[32] Univ Med Ctr Goettingen, Dept Med Stat, Gottingen, Germany

[33] Univ Edinburgh, Renal Med, Royal Infirm, Edinburgh, Midlothian, Scotland

[34] Univ Manchester, Wellcome Trust Ctr Cell Matrix Res, Fac Life Sci, Manchester, Lancs, England

来源：

NEPHROLOGY DIALYSIS TRANSPLANTATION | 2017年 / 32卷 / 06期

基金：

英国惠康基金;

关键词：

Alport syndrome; chronic kidney disease; guidelines; hereditary kidney disease; nephroprotection; DYSTROPHIC EPIDERMOLYSIS-BULLOSA; RENAL-FAILURE; HEARING-LOSS; INNER-EAR; EDUCATIONAL-ATTAINMENT; CYSTIC-FIBROSIS; CIRCADIAN CLOCK; KIDNEY-DISEASE; BLOOD-PRESSURE; COLLAGEN;

D O I：

10.1093/ndt/gfw095

中图分类号：

R3 [基础医学]; R4 [临床医学];

学科分类号：

1001 ; 1002 ; 100602 ;

摘要：

Alport syndrome (AS) is a genetic disease characterized by haematuric glomerulopathy variably associated with hearing loss and anterior lenticonus. It is caused by mutations in the COL4A3, COL4A4 or COL4A5 genes encoding the alpha 3 alpha 4 alpha 5(IV) collagen heterotrimer. AS is rare, but it accounts for > 1% of patients receiving renal replacement therapy. Angiotensin-converting enzyme inhibition slows, but does not stop, the progression to renal failure; therefore, there is an urgent requirement to expand and intensify research towards discovering new therapeutic targets and new therapies. The 2015 International Workshop on Alport Syndrome targeted unmet needs in basic science, genetics and diagnosis, clinical research and current clinical care. In three intensive days, more than 100 international experts including physicians, geneticists, researchers from academia and industry, and patient representatives from all over the world participated in panel discussions and breakout groups. This report summarizes the most important priority areas including (i) understanding the crucial role of podocyte protection and regeneration, (ii) targeting mutations by new molecular techniques for new animal models and potential gene therapy, (iii) creating optimal interaction between nephrologists and geneticists for early diagnosis, (iv) establishing standards for mutation screening and databases, (v) improving widespread accessibility to current standards of clinical care, (vi) improving collaboration with the pharmaceutical/biotech industry to investigate new therapies, (vii) research in hearing loss as a huge unmet need in Alport patients and (viii) the need to evaluate the risk and benefit of novel (including 'repurposing') therapies on an international basis.

引用

页码：916 / 924

页数：9

共 16 条

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