Truncation of POC1A associated with short stature and extreme insulin resistance

Journal of Molecular Endocrinology
Jian-Hua ChenInês Barroso

Abstract

We describe a female proband with primordial dwarfism, skeletal dysplasia, facial dysmorphism, extreme dyslipidaemic insulin resistance and fatty liver associated with a novel homozygous frameshift mutation in POC1A, predicted to affect two of the three protein products of the gene. POC1A encodes a protein associated with centrioles throughout the cell cycle and implicated in both mitotic spindle and primary ciliary function. Three homozygous mutations affecting all isoforms of POC1A have recently been implicated in a similar syndrome of primordial dwarfism, although no detailed metabolic phenotypes were described. Primary cells from the proband we describe exhibited increased centrosome amplification and multipolar spindle formation during mitosis, but showed normal DNA content, arguing against mitotic skipping, cleavage failure or cell fusion. Despite evidence of increased DNA damage in cells with supernumerary centrosomes, no aneuploidy was detected. Extensive centrosome clustering both at mitotic spindles and in primary cilia mitigated the consequences of centrosome amplification, and primary ciliary formation was normal. Although further metabolic studies of patients with POC1A mutations are warranted, we suggest that POC1...Continue Reading

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Citations

Jan 23, 2016·Journal of Human Genetics·Jung Min KoTae-Joon Cho
Jun 3, 2016·Molecular Biology of the Cell·Janet B MeehlMark Winey
Aug 19, 2017·European Journal of Endocrinology·Elisa GiorgioAlfredo Brusco
Dec 21, 2018·American Journal of Medical Genetics. Part a·Ken SaidaNaomichi Matsumoto
Nov 14, 2018·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Tom Hearn

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