FAM92A Underlies Nonsyndromic Postaxial Polydactyly in Humans and an Abnormal Limb and Digit Skeletal Phenotype in Mice.
CHIBBY1
CILIOPATHY
FAM92A
PAPA
POSTAXIAL POLYDACTYLY
Journal
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
ISSN: 1523-4681
Titre abrégé: J Bone Miner Res
Pays: United States
ID NLM: 8610640
Informations de publication
Date de publication:
02 2019
02 2019
Historique:
received:
30
04
2018
revised:
09
09
2018
accepted:
22
09
2018
pubmed:
6
11
2018
medline:
28
5
2020
entrez:
6
11
2018
Statut:
ppublish
Résumé
Polydactyly is a common congenital anomaly of the hand and foot. Postaxial polydactyly (PAP) is characterized by one or more posterior or postaxial digits. In a Pakistani family with autosomal recessive nonsyndromic postaxial polydactyly type A (PAPA), we performed genomewide genotyping, linkage analysis, and exome and Sanger sequencing. Exome sequencing revealed a homozygous nonsense variant (c.478C>T, p.[Arg160*]) in the FAM92A gene within the mapped region on 8q21.13-q24.12 that segregated with the PAPA phenotype. We found that FAM92A is expressed in the developing mouse limb and E11.5 limb bud including the progress zone and the apical ectodermal ridge, where it strongly localizes at the cilia level, suggesting an important role in limb patterning. The identified variant leads to a loss of the FAM92A/Chibby1 complex that is crucial for ciliogenesis and impairs the recruitment and the colocalization of FAM92A with Chibby1 at the base of the cilia. In addition, we show that Fam92a
Identifiants
pubmed: 30395363
doi: 10.1002/jbmr.3594
pmc: PMC6489482
mid: NIHMS1013181
doi:
Substances chimiques
CBY1 protein, human
0
CIBAR1 protein, human
0
Carrier Proteins
0
Chibby protein, mouse
0
Codon, Nonsense
0
Nuclear Proteins
0
Proteins
0
Types de publication
Clinical Trial
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
375-386Subventions
Organisme : NHGRI NIH HHS
ID : UM1 HG006348
Pays : United States
Organisme : NHGRI NIH HHS
ID : U54 HG006348
Pays : United States
Organisme : NHGRI NIH HHS
ID : UM1 HG006493
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK114356
Pays : United States
Organisme : NIDCD NIH HHS
ID : R01 DC016295
Pays : United States
Informations de copyright
© 2018 American Society for Bone and Mineral Research.
Références
J Med Genet. 2018 Jul;55(7):479-488
pubmed: 29572253
Nat Genet. 2018 Mar;50(3):460-471
pubmed: 29459677
Genome Res. 2010 Sep;20(9):1297-303
pubmed: 20644199
Mutat Res Rev Mutat Res. 2014 Oct-Dec;762:52-64
pubmed: 25485595
Nat Genet. 2000 May;25(1):25-9
pubmed: 10802651
Sci Rep. 2016 Sep 26;6:34232
pubmed: 27666822
Am J Hum Genet. 1998 Jul;63(1):259-66
pubmed: 9634505
J Med Genet. 2013 Jan;50(1):47-53
pubmed: 23160277
Dev Dyn. 2011 May;240(5):931-42
pubmed: 21445961
Nat Genet. 2016 Sep;48(9):1071-6
pubmed: 27428751
Front Pediatr. 2015 Feb 11;3:8
pubmed: 25717468
Am J Hum Genet. 1999 Sep;65(3):645-55
pubmed: 10441570
Eur J Hum Genet. 2006 Oct;14(10):1074-81
pubmed: 16757948
Nucleic Acids Res. 2002 Jan 1;30(1):207-10
pubmed: 11752295
Cell. 2013 Jul 18;154(2):452-64
pubmed: 23870131
Hum Genet. 2012 Mar;131(3):415-22
pubmed: 21877132
Nucleic Acids Res. 2017 Jan 4;45(D1):D183-D189
pubmed: 27899595
Structure. 2011 Jul 13;19(7):955-66
pubmed: 21742262
Bioinformatics. 2010 Mar 1;26(5):589-95
pubmed: 20080505
Am J Med Genet. 1998 Dec 28;80(5):459-65
pubmed: 9880209
CSH Protoc. 2006 Jun 01;2006(1):
pubmed: 22485786
Am J Med Genet A. 2007 Dec 15;143A(24):3150-60
pubmed: 18000979
Hum Mol Genet. 2016 Sep 15;25(18):4012-4020
pubmed: 27466190
Nature. 2016 Aug 17;536(7616):285-91
pubmed: 27535533
Nucleic Acids Res. 2010 Sep;38(16):e164
pubmed: 20601685
Nature. 2011 Jun 15;474(7351):337-42
pubmed: 21677750
Annu Rev Biochem. 2007;76:51-74
pubmed: 17352659
Nat Genet. 2002 Jan;30(1):97-101
pubmed: 11731797
Nature. 2012 Sep 6;489(7414):57-74
pubmed: 22955616
Birth Defects Res A Clin Mol Teratol. 2010 Aug;88(8):633-52
pubmed: 20544799
Nucleic Acids Res. 2012 Jul;40(Web Server issue):W516-20
pubmed: 22669902
Nat Genet. 2000 May;25(1):12-3
pubmed: 10802644
Nucleic Acids Res. 2014 Jan;42(Database issue):D802-9
pubmed: 24194600
Eur J Hum Genet. 2003 May;11(5):409-15
pubmed: 12734547
Dev Cell. 2014 Mar 10;28(5):483-96
pubmed: 24582806
Eur J Hum Genet. 2017 Aug;25(8):960-965
pubmed: 28488682
Eur J Hum Genet. 2002 Mar;10(3):162-6
pubmed: 11973619
Eur J Med Genet. 2010 Jan-Feb;53(1):45-9
pubmed: 19941983
Nat Genet. 2014 Mar;46(3):310-5
pubmed: 24487276
Mol Biol Cell. 2017 Feb 1;28(3):463-475
pubmed: 27932498
Mol Cell Biol. 2016 Oct 13;36(21):2668-2680
pubmed: 27528616
Am J Hum Genet. 1997 Mar;60(3):597-604
pubmed: 9042919
Hum Mol Genet. 2015 Jul 15;24(14):4103-13
pubmed: 25911677
J Clin Invest. 2018 Apr 2;128(4):1509-1522
pubmed: 29408807
J Pediatr Genet. 2014 Jun;3(2):129-40
pubmed: 27625869