Mutations in C2orf37, Encoding a Nucleolar Protein, Cause Hypogonadism, Alopecia, Diabetes Mellitus, Mental Retardation, and Extrapyramidal Syndrome

被引：95

作者：

Alazami, Anas M. ^{[1
]}

Al-Saif, Amr ^{[1
]}

Al-Semari, Abdulaziz ^{[2
]}

Bohlega, Saeed ^{[2
]}

Zlitni, Soumaya ^{[1
]}

Alzahrani, Fatema ^{[1
]}

Bavi, Prashant ^{[3
]}

Kaya, Namik ^{[1
]}

Colak, Dilek ^{[4
]}

Khalak, Hanif ^{[1
]}

Baltus, Andy ^{[5
,6
]}

Peterlin, Borut ^{[7
]}

Danda, Sumita ^{[8
]}

Bhatia, Kailash P. ^{[9
]}

Schneider, Susanne A. ^{[9
]}

Sakati, Nadia ^{[10
]}

Walsh, Christopher A. ^{[5
,6
]}

Al-Mohanna, Futwan ^{[11
]}

Meyer, Brian ^{[1
]}

Alkuraya, Fowzan S. ^{[1
,5
,6
,12
,13
]}

机构：

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

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

[3] King Faisal Specialist Hosp & Res Ctr, Biol Repository Sect, Riyadh 11211, Saudi Arabia

[4] King Faisal Specialist Hosp & Res Ctr, Dept Biostat & Sci Comp, Riyadh 11211, Saudi Arabia

[5] Childrens Hosp, Dept Med, Div Genet & Metab, Boston, MA 02115 USA

[6] Harvard Univ, Sch Med, Boston, MA 02115 USA

[7] Univ Med Ctr Ljubljana, Dept Obstet & Gynecol, Inst Med Genet, Ljubljana 1000, Slovenia

[8] Christian Med Coll & Hosp, Clin Genet Unit, Vellore 632004, Tamil Nadu, India

[9] UCL, Inst Neurol, Sobell Dept, London WC1N 3BG, England

[10] King Faisal Specialist Hosp & Res Ctr, Dept Pediat, Riyadh 11211, Saudi Arabia

[11] King Faisal Specialist Hosp & Res Ctr, Dept Cell Biol, Riyadh 11211, Saudi Arabia

[12] King Saud Univ, King Khalid Univ Hosp, Dept Pediat, Riyadh 11461, Saudi Arabia

[13] King Saud Univ, Coll Med, Riyadh 11461, Saudi Arabia

来源：

AMERICAN JOURNAL OF HUMAN GENETICS | 2008年 / 83卷 / 06期

关键词：

D O I：

10.1016/j.ajhg.2008.10.018

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Hypogonadism, alopecia, diabetes mellitus, mental retardation, and extrapyramidal syndrome (also referenced as Woodhouse-Sakati syndrome) is a rare autosomal recessive multisystemic disorder. We have identified a founder mutation consisting of a single base-pair deletion in C2orf37 in eight families of Saudi origin. Three other loss-of-function mutations were subsequently discovered in patients of different ethnicities. The gene encodes a nucleolar protein of unknown function, and the cellular phenotype observed in patient lymphoblasts implicates a role for the nucleolus in the pathogenesis of this disease. Our findings expand the list of human disorders linked to the nucleolus and further highlight the developmental and/or maintenance functions of this organelle.

引用

页码：684 / 691

页数：8

共 12 条

[1] Autosomal-recessive syndrome with alopecia, hypogonadism, progressive extra-pyramidal disorder, white matter disease, sensory neural deafness, diabetes mellitus, and low IGF1 [J].

Al-Semari, Abdulaziz ;

Bohlega, Saeed .

AMERICAN JOURNAL OF MEDICAL GENETICS PART A, 2007, 143A (02) :149-160

[2] The multifunctional nucleolus [J].

Boisvert, Francois-Michel ;

van Koningsbruggen, Silvana ;

Navascues, Joaquin ;

Lamond, Angus I. .

NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2007, 8 (07) :574-585

[3] Initiation of nucleolar assembly is independent of RNA polymerase I transcription [J].

Dousset, T ;

Wang, C ;

Verheggen, C ;

Chen, DY ;

Hernandez-Verdun, D ;

Huang, S .

MOLECULAR BIOLOGY OF THE CELL, 2000, 11 (08) :2705-2717

[4] Estimating the age of rare disease mutations: the example of Triple-A syndrome [J].

Genin, E ;

Tullio-Pelet, A ;

Begeot, F ;

Lyonnet, S ;

Abel, L .

JOURNAL OF MEDICAL GENETICS, 2004, 41 (06) :445-449

[5] Nucleophosmin is a novel Bax chaperone that regulates apoptotic cell death [J].

Kerr, L. E. ;

Birse-Archbold, J-L A. ;

Short, D. M. ;

McGregor, A. L. ;

Heron, I. ;

MacDonald, D. C. ;

Thompson, J. ;

Carlson, G. J. ;

Kelly, J. S. ;

McCulloch, J. ;

Sharkey, J. .

ONCOGENE, 2007, 26 (18) :2554-2562

[6] Three siblings with Woodhouse-Sakati syndrome in an Indian family [J].

Koshy, George ;

Danda, Sumita ;

Thomas, Nihal ;

Mathews, Vikram ;

Viswanathan, Vijay .

CLINICAL DYSMORPHOLOGY, 2008, 17 (01) :57-60

[7]

MEdica I, 2007, GENET COUNSEL, V18, P227

[8] Alopecia, neurological defects, and endocrinopathy syndrome caused by decreased expression of RBM28, a nucleolar protein associated with ribosome biogenesis [J].

Nousbeck, Janna ;

Spiegel, Ronen ;

Ishida-Yamamoto, Akemi ;

Indelman, Margarita ;

Shani-Adir, Ayelet ;

Adir, Noam ;

Lipkin, Ehud ;

Bercovici, Sivan ;

Geiger, Dan ;

van Steensel, Maurice A. ;

Steijlen, Peter M. ;

Bergman, Reuven ;

Bindereif, Albrecht ;

Choder, Mordechai ;

Shalev, Stavit ;

Sprecher, Eli .

AMERICAN JOURNAL OF HUMAN GENETICS, 2008, 82 (05) :1114-1121

[9] NUCLEOLOGENESIS - COMPOSITION AND FATE OF PRENUCLEOLAR BODIES [J].

OCHS, RL ;

LISCHWE, MA ;

SHEN, E ;

CARROLL, RE ;

BUSCH, H .

CHROMOSOMA, 1985, 92 (05) :330-336

[10] Dystonia in the Woodhouse Sakati syndrome: A new family and literature review [J].

Schneider, Susanne A. ;

Bhatia, Kailash P. .

MOVEMENT DISORDERS, 2008, 23 (04) :592-596

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