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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Am+J+Hum+Genet
2017 ; 100
(1
): 21-30
Nephropedia Template TP
gab.com Text
Twit Text FOAVip
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English Wikipedia
Loss-of-Function Mutations in YY1AP1 Lead to Grange Syndrome and a Fibromuscular
Dysplasia-Like Vascular Disease
#MMPMID27939641
Guo DC
; Duan XY
; Regalado ES
; Mellor-Crummey L
; Kwartler CS
; Kim D
; Lieberman K
; de Vries BBA
; Pfundt R
; Schinzel A
; Kotzot D
; Shen X
; Yang ML
; Bamshad MJ
; Nickerson DA
; Gornik HL
; Ganesh SK
; Braverman AC
; Grange DK
; Milewicz DM
Am J Hum Genet
2017[Jan]; 100
(1
): 21-30
PMID27939641
show ga
Fibromuscular dysplasia (FMD) is a heterogeneous group of non-atherosclerotic and
non-inflammatory arterial diseases that primarily involves the renal and
cerebrovascular arteries. Grange syndrome is an autosomal-recessive condition
characterized by severe and early-onset vascular disease similar to FMD and
variable penetrance of brachydactyly, syndactyly, bone fragility, and learning
disabilities. Exome-sequencing analysis of DNA from three affected siblings with
Grange syndrome identified compound heterozygous nonsense variants in YY1AP1, and
homozygous nonsense or frameshift YY1AP1 variants were subsequently identified in
additional unrelated probands with Grange syndrome. YY1AP1 encodes yin yang 1
(YY1)-associated protein 1 and is an activator of the YY1 transcription factor.
We determined that YY1AP1 localizes to the nucleus and is a component of the
INO80 chromatin remodeling complex, which is responsible for transcriptional
regulation, DNA repair, and replication. Molecular studies revealed that loss of
YY1AP1 in vascular smooth muscle cells leads to cell cycle arrest with decreased
proliferation and increased levels of the cell cycle regulator p21/WAF/CDKN1A and
disrupts TGF-?-driven differentiation of smooth muscle cells. Identification of
YY1AP1 mutations as a cause of FMD indicates that this condition can result from
underlying genetic variants that significantly alter the phenotype of vascular
smooth muscle cells.