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Loss of LDAH associated with prostate cancer and hearing loss.

Abstract：

:Great strides in gene discovery have been made using a multitude of methods to associate phenotypes with genetic variants, but there still remains a substantial gap between observed symptoms and identified genetic defects. Herein, we use the convergence of various genetic and genomic techniques to investigate the underpinnings of a constellation of phenotypes that include prostate cancer (PCa) and sensorineural hearing loss (SNHL) in a human subject. Through interrogation of the subject's de novo, germline, balanced chromosomal translocation, we first identify a correlation between his disorders and a poorly annotated gene known as lipid droplet associated hydrolase (LDAH). Using data repositories of both germline and somatic variants, we identify convergent genomic evidence that substantiates a correlation between loss of LDAH and PCa. This correlation is validated through both in vitro and in vivo models that show loss of LDAH results in increased risk of PCa and, to a lesser extent, SNHL. By leveraging convergent evidence in emerging genomic data, we hypothesize that loss of LDAH is involved in PCa and other phenotypes observed in support of a genotype-phenotype association in an n-of-one human subject.

journal_name

Hum Mol Genet

journal_title

Human molecular genetics

authors

Currall BB,Chen M,Sallari RC,Cotter M,Wong KE,Robertson NG,Penney KL,Lunardi A,Reschke M,Hickox AE,Yin Y,Wong GT,Fung J,Brown KK,Williamson RE,Sinnott-Armstrong NA,Kammin T,Ivanov A,Zepeda-Mendoza CJ,Shen J,Quade

doi

10.1093/hmg/ddy310

subject

Has Abstract

pub_date

2018-12-15 00:00:00

pages

4194-4203

issue

24

eissn

0964-6906

issn

1460-2083

pii

5087742

journal_volume

27

pub_type

杂志文章

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