A specific mutation in TBL1XR1 causes Pierpont syndrome

Journal of Medical Genetics
Charlotte A HeinenRaoul C Hennekam

Abstract

The combination of developmental delay, facial characteristics, hearing loss and abnormal fat distribution in the distal limbs is known as Pierpont syndrome. The aim of the present study was to detect and study the cause of Pierpont syndrome. We used whole-exome sequencing to analyse four unrelated individuals with Pierpont syndrome, and Sanger sequencing in two other unrelated affected individuals. Expression of mRNA of the wild-type candidate gene was analysed in human postmortem brain specimens, adipose tissue, muscle and liver. Expression of RNA in lymphocytes in patients and controls was additionally analysed. The variant protein was expressed in, and purified from, HEK293 cells to assess its effect on protein folding and function. We identified a single heterozygous missense variant, c.1337A>G (p.Tyr446Cys), in transducin β-like 1 X-linked receptor 1 (TBL1XR1) as disease-causing in all patients. TBL1XR1 mRNA expression was demonstrated in pituitary, hypothalamus, white and brown adipose tissue, muscle and liver. mRNA expression is lower in lymphocytes of two patients compared with the four controls. The mutant TBL1XR1 protein assembled correctly into the nuclear receptor corepressor (NCoR)/ silencing mediator for retinoid...Continue Reading

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Citations

May 3, 2016·American Journal of Medical Genetics. Part a·Christine M ArmourKym M Boycott
Oct 21, 2016·American Journal of Medical Genetics. Part a·Yu SunYongguo Yu
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Methods Mentioned

BETA
PCR
Exome Sequencing
transfections
transfection
biopsies
gastric bypass
electrophoresis

Software Mentioned

KGGSeq
Lifescope aligner
LinReg
GATK
Genome Analysis Toolkit ( GATK2
Lifescope
Picard Tools

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