title: Functional variants of POC5 identified in patients with idiopathic scoliosis.
abstract: Idiopathic scoliosis (IS) is a spine deformity that affects approximately 3% of the population. The underlying causes of IS are not well understood, although there is clear evidence that there is a genetic component to the disease. Genetic mapping studies suggest high genetic heterogeneity, but no IS disease-causing gene has yet been identified. Here, genetic linkage analyses combined with exome sequencing identified a rare missense variant (p.A446T) in the centriolar protein gene POC5 that cosegregated with the disease in a large family with multiple members affected with IS. Subsequently, the p.A446T variant was found in an additional set of families with IS and in an additional 3 cases of IS. Moreover, POC5 variant p.A455P was present and linked to IS in one family and another rare POC5 variant (p.A429V) was identified in an additional 5 cases of IS. In a zebrafish model, expression of any of the 3 human IS-associated POC5 variant mRNAs resulted in spine deformity, without affecting other skeletal structures. Together, these findings indicate that mutations in the POC5 gene contribute to the occurrence of IS.
authors: Shunmoogum A
authors: SA
authors: Patten
authors: Patricia
authors: P
authors: Margaritte-Jeannin
authors: Jean-Claude
authors: JC
authors: Bernard
authors: Eudeline
authors: E
authors: Alix
authors: Audrey
authors: A
authors: Labalme
authors: Alicia
authors: A
authors: Besson
authors: Simon L
authors: SL
authors: Girard
authors: Khaled
authors: K
authors: Fendri
authors: Nicolas
authors: N
authors: Fraisse
authors: Bernard
authors: B
authors: Biot
authors: Coline
authors: C
authors: Poizat
authors: Amandine
authors: A
authors: Campan-Fournier
authors: Kariman
authors: K
authors: Abelin-Genevois
authors: Vincent
authors: V
authors: Cunin
authors: Charlotte
authors: C
authors: Zaouter
authors: Meijiang
authors: M
authors: Liao
authors: Raphaelle
authors: R
authors: Lamy
authors: Gaetan
authors: G
authors: Lesca
authors: Rita
authors: R
authors: Menassa
authors: Charles
authors: C
authors: Marcaillou
authors: Melanie
authors: M
authors: Letexier
authors: Damien
authors: D
authors: Sanlaville
authors: Jerome
authors: J
authors: Berard
authors: Guy A
authors: GA
authors: Rouleau
authors: Françoise
authors: F
authors: Clerget-Darpoux
authors: Pierre
authors: P
authors: Drapeau
authors: Florina
authors: F
authors: Moldovan
authors: Patrick
authors: P
authors: Edery
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics*; D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D020125:Mutation, Missense; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D012600:Scoliosis / Q000235:genetics*; D015027:Zebrafish
chemical_list: D002352:Carrier Proteins; C540807:POC5 protein, human
references: Nat Genet. 2011 Dec;43(12):1237-40
references: 22019779
references: J Cell Biol. 2013 Mar 4;200(5):667-79
references: 23460678
references: Clin Orthop Relat Res. 1972 Jul-Aug;86:121-31
references: 5047777
references: J Med Genet. 2008 Feb;45(2):87-92
references: 17932119
references: Clin Orthop Relat Res. 2007 Sep;462:6-10
references: 17603389
references: PLoS One. 2013;8(7):e68487
references: 23844208
references: Br Med J. 1934 Feb 24;1(3816):328
references: 20778092
references: J Clin Invest. 2012 Jul;122(7):2337-43
references: 22751109
references: Hum Mol Genet. 2011 Apr 1;20(7):1456-66
references: 21216876
references: Spine (Phila Pa 1976). 2000 Sep 15;25(18):2372-80
references: 10984791
references: Nat Genet. 2013 Jun;45(6):676-9
references: 23666238
references: Clin Orthop Relat Res. 1977 Jul-Aug;(126):17-25
references: 598109
references: Spine (Phila Pa 1976). 2006 Jul 15;31(16):1815-9
references: 16845357
references: Eur J Hum Genet. 2011 Aug;19(8):865-9
references: 21407261
references: Chir Narzadow Ruchu Ortop Pol. 1976;41(2):161-5
references: 1269331
references: J Bone Joint Surg Br. 1968 Feb;50(1):24-30
references: 5641594
references: Perspect Dev Neurobiol. 1997;5(1):3-16
references: 9509514
references: J Cell Biol. 2009 Apr 6;185(1):101-14
references: 19349582