Ciliopathies A reference for clinicians

Abstract

This is a multi-author book encompassing 14 chapters on diseases associated with defects in proteins expressed in the primary cilia, a structure long regarded as a useless vestigial organelle. The first chapter covers our current knowledge of the structure and biology of the motile and non-motile (primary) cilia and proposes a clinical diagnosis algorithm. Further chapters deal with the Alstrom, Jeune, Joubert, Bardet-Biedl, Meckel-Gruber, OFDI and Usher syndromes as well as Leber congenital amaurosis, nephronophtisis, autosomal-dominant and -recessive polycystic kidney diseases and primary ciliary dyskinesia. All chapters follow the same format: a history of the eponym, epidemiology, clinical features, range of the phenotype, diagnosis, genetics, underlying ciliary defect and physiological effect and clinical management of the defect. The last section is dedicated to syndromes not yet proven to be ciliopathies. This book is a welcome contribution, as our knowledge about cilia and ciliopathies has been growing very fast in the past decade, even if probably only the tip of the iceberg has been revealed. As cilia are found on nearly every cell of our body and play a crucial role in the development and function of many organs, ciliopathies cover many fields of medicine. This work is particularly valuable in that, for the first time, it brings together known ciliopathies, some of which are only encountered by geneticists and others by paediatricians, nephrologists or ophthalmologists. This book provides a nice updated review for each syndrome or disease. The different phenotypes associated with mutations of the same genes are clearly presented, even if the book does not highlight the features that link these pathologies and the continuum bridging the broad range of phenotypes ranging from isolated Leber congenital amorosis to the severe Meckel-Gruber syndrome. Given the range of phenotypes which can arise from a mutation in the same gene, it is not surprising that there is a considerable overlap between each of the chapters. Unfortunately, the book lacks a chapter providing synthetic information and illustrations regarding the role of cilia in signalling. Also, the key involvement of cilia in development, in the cell cycle and possibly in cancer is not addressed. A few critical remarks should be included in this review. Should the authors consider writing a new edition, they should consider including HNF1β in the list of genes involved in ciliopthies. The gene list in the introduction (Page xii) mentions that CEP290 uncodes an uncharacterized protein. In fact, CEP, also called NPHP6 (Page xv), encodes 13 coiled-coil domains, SMC, NLS, 6 KID motifs, homology with tropomyosin and an ATP/GTP-binding motif. Also, the authors should note that PKHD1 is the gene for autosomal-recessive polycystic disease, not for autosomal-dominant polycystic kidney disease (Page 5). In Chapter 8, Table 8.1, the Mainzer-Saldino syndrome (nephronophthisis with cone-shaped epiphyses) is missing. Also in Chapter 8 on nephronophthisis, as far as the treatment is concerned, it is not obvious that treatments that are effective in reducing renal cysts in ADPKD will be effective in nephronophthisis as the progression to renal failure is mainly due to interstitial fibrosis while renal cysts develop late. The nephrologist will not find information in this publication regarding the mechanisms of fibrosis in nephronophtisis, however, he will realize how important the search is for extra-renal symptoms in patients affected with nephronophtisis or with renal cystic diseases, for the best care and support of the patients. Overall, this book can be highly recommended to every nephrologist, paediatrician and ophthalmologist.