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. 2020 Jun;22(6):1051-1060.
doi: 10.1038/s41436-020-0761-1. Epub 2020 Feb 14.

The morbid genome of ciliopathies: an update

Hanan E Shamseldin  1 , Ranad Shaheen  1 , Nour Ewida  1 , Dalal K Bubshait  2 , Hisham Alkuraya  3 , Elham Almardawi  4 , Ali Howaidi  1 , Yasser Sabr  5 , Ebtesam M Abdalla  6 , Abdullah Y Alfaifi  7 , Jameel Mohammed Alghamdi  8 , Afaf Alsagheir  9 , Ahmed Alfares  10 , Heba Morsy  6 , Maged H Hussein  11 , Mohammad A Al-Muhaizea  12 , Mohammad Shagrani  13 , Essam Al Sabban  14 , Mustafa A Salih  15 , Neama Meriki  4 , Rubina Khan  16 , Maisoon Almugbel  16 , Alya Qari  17 , Maha Tulba  16 , Mohammed Mahnashi  18 , Khalid Alhazmi  18 , Abrar K Alsalamah  19 , Sawsan R Nowilaty  19 , Amal Alhashem  10   20 , Mais Hashem  1 , Firdous Abdulwahab  1 , Niema Ibrahim  1 , Tarfa Alshidi  1 , Eman AlObeid  1 , Mona M Alenazi  1 , Hamad Alzaidan  17 , Zuhair Rahbeeni  17 , Mohammed Al-Owain  17 , Sameera Sogaty  21 , Mohammed Zain Seidahmed  7 , Fowzan S Alkuraya  22   23   24
Affiliations
Free article

The morbid genome of ciliopathies: an update

Hanan E Shamseldin et al. Genet Med. 2020 Jun.
Free article

Erratum in

  • The morbid genome of ciliopathies: an update.
    Shamseldin HE, Shaheen R, Ewida N, Bubshait DK, Alkuraya H, Almardawi E, Howaidi A, Sabr Y, Abdalla EM, Alfaifi AY, Mohammed Alghamdi J, Alsagheir A, Alfares A, Morsy H, Hussein MH, Al-Muhaizea MA, Shagrani M, Al Sabban E, Salih MA, Meriki N, Khan R, Almugbel M, Qari A, Tulba M, Mahnashi M, Alhazmi K, Alsalamah AK, Nowilaty SR, Alhashem A, Hashem M, Abdulwahab F, Ibrahim N, Alshidi T, AlObeid E, Alenazi MM, Alzaidan H, Rahbeeni Z, Al-Owain M, Sogaty S, Zain Seidahmed M, Alkuraya FS. Shamseldin HE, et al. Genet Med. 2022 Apr;24(4):966. doi: 10.1016/j.gim.2022.01.019. Genet Med. 2022. PMID: 35394428 No abstract available.

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.

Keywords: Stargardt; allelism; noncoding; oligogenic; Blended Phenotype.

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