학술논문
The morbid genome of ciliopathies: an update
Document Type
Original Paper
Author
Shamseldin, Hanan E.; Shaheen, Ranad; Ewida, Nour; Bubshait, Dalal K.; Alkuraya, Hisham; Almardawi, Elham; Howaidi, Ali; Sabr, Yasser; Abdalla, Ebtesam M.; Alfaifi, Abdullah Y.; Alghamdi, Jameel Mohammed; Alsagheir, Afaf; Alfares, Ahmed; Morsy, Heba; Hussein, Maged H.; Al–Muhaizea, Mohammad A.; Shagrani, Mohammad; Al Sabban, Essam; Salih, Mustafa A.; Meriki, Neama; Khan, Rubina; Almugbel, Maisoon; Qari, Alya; Tulba, Maha; Mahnashi, Mohammed; Alhazmi, Khalid; Alsalamah, Abrar K.; Nowilaty, Sawsan R.; Alhashem, Amal; Hashem, Mais; Abdulwahab, Firdous; Ibrahim, Niema; Alshidi, Tarfa; AlObeid, Eman; Alenazi, Mona M.; Alzaidan, Hamad; Rahbeeni, Zuhair; Al–Owain, Mohammed; Sogaty, Sameera; Seidahmed, Mohammed Zain; Alkuraya, Fowzan S.
Source
Genetics in Medicine: Official journal of the American College of Medical Genetics and Genomics. 22(6):1051-1060
Subject
Language
English
ISSN
1098-3600
1530-0366
1530-0366
Abstract
Purpose: Ciliopathies are highly heterogeneous clinical disorders of the primary cilium. We aim to characterize a large cohort of ciliopathies phenotypically and molecularly.Methods: Detailed phenotypic and genomic analysis of patients with ciliopathies, and functional characterization of novel candidate genes.Results: In this study, we describe 125 families with ciliopathies and show that deleterious variants in previously reported genes, including cryptic splicing variants, account for 87% of cases. Additionally, we further support a number of previously reported candidate genes (BBIP1, MAPKBP1, PDE6D, and WDPCP), and propose nine novel candidate genes (CCDC67, CCDC96, CCDC172, CEP295, FAM166B, LRRC34, TMEM17, TTC6, and TTC23), three of which (LRRC34, TTC6, and TTC23) are supported by functional assays that we performed on available patient-derived fibroblasts. From a phenotypic perspective, we expand the phenomenon of allelism that characterizes ciliopathies by describing novel associations including WDR19-related Stargardt disease and SCLT1- and CEP164-related Bardet–Biedl syndrome.Conclusion: In this cohort of phenotypically and molecularly characterized ciliopathies, we draw important lessons that inform the clinical management and the diagnostics of this class of disorders as well as their basic biology.