IFT27, encoding a small GTPase component of IFT particles, is mutated in a consanguineous family with Bardet-Biedl syndrome

被引：109

作者：

Aldahmesh, Mohammed A. ^{[1
]}

Li, Yuanyuan ^{[3
]}

Alhashem, Amal ^{[5
,9
]}

Anazi, Shams ^{[1
]}

Alkuraya, Hisham ^{[6
]}

Hashem, Mais ^{[1
]}

Awaji, Ali A. ^{[7
]}

Sogaty, Sameera ^{[11
]}

Alkharashi, Abdullah ^{[8
]}

Alzahrani, Saeed ^{[12
]}

Al Hazzaa, Selwa A. ^{[2
,10
]}

Xiong, Yong ^{[4
]}

Kong, Shanshan ^{[3
]}

Sun, Zhaoxia ^{[2
,3
]}

Alkuraya, Fowzan S. ^{[1
,9
]}

机构：

[1] King Faisal Specialist Hosp & Res Ctr, Dept Genet, Riyadh 11211, Saudi Arabia

[2] King Faisal Specialist Hosp & Res Ctr, Dept Ophthalmol, Riyadh 11211, Saudi Arabia

[3] Yale Univ, Dept Genet, New Haven, CT USA

[4] Yale Univ, Dept Mol Biophys & Biochem, New Haven, CT USA

[5] Prince Sultan Mil Med City, Deparment Pediat, Riyadh, Saudi Arabia

[6] Imam Muhammad Ibn Saud Islamic Univ, Dept Ophthalmol, Coll Med, Riyadh, Saudi Arabia

[7] King Fahad Cent Hosp, Dept Pediat, Jazan, Saudi Arabia

[8] King Saud Univ, Coll Med, Deparment Ophthalmol, Riyadh 11461, Saudi Arabia

[9] Alfaisal Univ, Dept Anat & Cell Biol, Coll Med, Riyadh, Saudi Arabia

[10] Alfaisal Univ, Dept Ophthalmol, Coll Med, Riyadh, Saudi Arabia

[11] King Fahad Gen Hosp, Dept Med Genet, Jeddah, Saudi Arabia

[12] Prince Sultan Mil Med City, Dept Pediat Nephrol, Riyadh, Saudi Arabia

来源：

HUMAN MOLECULAR GENETICS | 2014年 / 23卷 / 12期

关键词：

SYNDROME GENES; MUTATIONS; PROTEINS; BBSOME; COMPLEX; IDENTIFICATION; FLAGELLAR; OBESITY; TRAFFICKING; DYSTROPHY;

D O I：

10.1093/hmg/ddu044

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Bardet-Biedl syndrome (BBS) is an autosomal recessive ciliopathy with multisystem involvement. So far, 18 BBS genes have been identified and the majority of them are essential for the function of BBSome, a protein complex involved in transporting membrane proteins into and from cilia. Yet defects in the identified genes cannot account for all the BBS cases. The genetic heterogeneity of this disease poses significant challenge to the identification of additional BBS genes. In this study, we coupled human genetics with functional validation in zebrafish and identified IFT27 as a novel BBS gene (BBS19). This is the first time an intraflagellar transport (IFT) gene is implicated in the pathogenesis of BBS, highlighting the genetic complexity of this disease.

引用

页码：3307 / 3315

页数：9

共 60 条

[1] Clinical and molecular characterisation of Bardet-Biedl syndrome in consanguineous populations: the power of homozygosity mapping [J].

Abu Safieh, L. ;

Aldahmesh, M. A. ;

Shamseldin, H. ;

Hashem, M. ;

Shaheen, R. ;

Alkuraya, H. ;

Al Hazzaa, S. A. F. ;

Al-Rajhi, A. ;

Alkuraya, F. S. .

JOURNAL OF MEDICAL GENETICS, 2010, 47 (04) :236-241

[2] In search of triallelism in Bardet-Biedl syndrome [J].

Abu-Safieh, Leen ;

Al-Anazi, Shamsa ;

Al-Abdi, Lama ;

Hashem, Mais ;

Alkuraya, Hisham ;

Alamr, Mushari ;

Sirelkhatim, Mugtaba O. ;

Al-Hassnan, Zuhair ;

Alkuraya, Basim ;

Mohamed, Jawahir Y. ;

Al-Salem, Ahmad ;

Alrashed, May ;

Faqeih, Eissa ;

Softah, Ameen ;

Al-Hashem, Amal ;

Wali, Sami ;

Rahbeeni, Zuhair ;

Alsayed, Moeen ;

Khan, Arif O. ;

Al-Gazali, Lihadh ;

Taschner, Peter E. M. ;

Al-Hazzaa, Selwa ;

Alkuraya, Fowzan S. .

EUROPEAN JOURNAL OF HUMAN GENETICS, 2012, 20 (04) :420-427

[3] The application of next-generation sequencing in the autozygosity mapping of human recessive diseases [J].

Alkuraya, Fowzan S. .

HUMAN GENETICS, 2013, 132 (11) :1197-1211

[4] Autozygome decoded [J].

Alkuraya, Fowzan S. .

GENETICS IN MEDICINE, 2010, 12 (12) :765-771

[5] Homozygosity mapping: One more tool in the clinical geneticist's toolbox [J].

Alkuraya, Fowzan S. .

GENETICS IN MEDICINE, 2010, 12 (04) :236-239

[6]

[Anonymous], DISCOVERY RARE HOMOZ

[7] Basal body dysfunction is a likely cause of pleiotropic Bardet-Biedl syndrome [J].

Ansley, SJ ;

Badano, JL ;

Blacque, OE ;

Hill, J ;

Hoskins, BE ;

Leitch, CC ;

Kim, JC ;

Ross, AJ ;

Eichers, ER ;

Teslovich, TM ;

Mah, AK ;

Johnsen, RC ;

Cavender, JC ;

Lewis, RA ;

Leroux, MR ;

Beales, PL ;

Katsanis, N .

NATURE, 2003, 425 (6958) :628-633

[8] C14ORF179 encoding IFT43 is mutated in Sensenbrenner syndrome [J].

Arts, Heleen H. ;

Bongers, Ernie M. H. F. ;

Mans, Dorus A. ;

van Beersum, Sylvia E. C. ;

Oud, Machteld M. ;

Bolat, Emine ;

Spruijt, Liesbeth ;

Cornelissen, Elisabeth A. M. ;

Schuurs-Hoeijmakers, Janneke H. M. ;

de Leeuw, Nicole ;

Cormier-Daire, Valerie ;

Brunner, Han G. ;

Knoers, Nine V. A. M. ;

Roepman, Ronald .

JOURNAL OF MEDICAL GENETICS, 2011, 48 (06) :390-395

[9] Identification of a novel Bardet-Biedl syndrome protein, BBS7, that shares structural features with BBS1 and BBS2 [J].

Badano, JL ;

Ansley, SJ ;

Leitch, CC ;

Lewis, RA ;

Lupski, JR ;

Katsanis, N .

AMERICAN JOURNAL OF HUMAN GENETICS, 2003, 72 (03) :650-658

[10] Automated server predictions in CASP7 [J].

Battey, James N. D. ;

Kopp, Jurgen ;

Bordoli, Lorenza ;

Read, Randy J. ;

Clarke, Neil D. ;

Schwede, Torsten .

PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS, 2007, 69 :68-82

← 1 2 3 4 5 6 →