title: POC1A truncation mutation causes a ciliopathy in humans characterized by primordial dwarfism.
abstract: Primordial dwarfism (PD) is a phenotype characterized by profound growth retardation that is prenatal in onset. Significant strides have been made in the last few years toward improved understanding of the molecular underpinning of the limited growth that characterizes the embryonic and postnatal development of PD individuals. These include impaired mitotic mechanics, abnormal IGF2 expression, perturbed DNA-damage response, defective spliceosomal machinery, and abnormal replication licensing. In three families affected by a distinct form of PD, we identified a founder truncating mutation in POC1A. This gene is one of two vertebrate paralogs of POC1, which encodes one of the most abundant proteins in the Chlamydomonas centriole proteome. Cells derived from the index individual have abnormal mitotic mechanics with multipolar spindles, in addition to clearly impaired ciliogenesis. siRNA knockdown of POC1A in fibroblast cells recapitulates this ciliogenesis defect. Our findings highlight a human ciliopathy syndrome caused by deficiency of a major centriolar protein.
authors: Department of Genetics, King Faisal Specialist Hospital and Research Center, P.O. Box 3354, Riyadh 11211, Saudi Arabia.
authors: Ranad
authors: R
authors: Shaheen
authors: Eissa
authors: E
authors: Faqeih
authors: Hanan E
authors: HE
authors: Shamseldin
authors: Ramil R
authors: RR
authors: Noche
authors: Asma
authors: A
authors: Sunker
authors: Muneera J
authors: MJ
authors: Alshammari
authors: Tarfa
authors: T
authors: Al-Sheddi
authors: Nouran
authors: N
authors: Adly
authors: Mohammed S
authors: MS
authors: Al-Dosari
authors: Sean G
authors: SG
authors: Megason
authors: Muneera
authors: M
authors: Al-Husain
authors: Futwan
authors: F
authors: Al-Mohanna
authors: Fowzan S
authors: FS
authors: Alkuraya
mesh_terms: D001483:Base Sequence; D018797:Cell Cycle Proteins; D002502:Centrioles / Q000235:genetics* / Q000378:metabolism; D002923:Cilia / Q000235:genetics* / Q000473:pathology; D003598:Cytoskeletal Proteins; D004392:Dwarfism / Q000235:genetics* / Q000473:pathology*; D005260:Female; D040461:Gene Components; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D010375:Pedigree; D011506:Proteins / Q000235:genetics*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D017422:Sequence Analysis, DNA; D008941:Spindle Apparatus / Q000235:genetics / Q000473:pathology
chemical_list: D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; C575745:POC1A protein, human; D011506:Proteins; D034741:RNA, Small Interfering