Estrogen-related receptor gamma implicated in a phenotype including hearing loss and mild developmental delay

Abstract

Analysis of chromosomal rearrangements has been highly successful in identifying genes involved in many congenital abnormalities including hearing loss. Herein, we report a subject, designated DGAP242, with congenital hearing loss (HL) and a de novo balanced translocation 46,XX,t(1;5)(q32;q15)dn. Using multiple next-generation sequencing techniques, we obtained high resolution of the breakpoints. This revealed disruption of the orphan receptor ESRRG on chromosome 1, which is differentially expressed in inner ear hair cells and has previously been implicated in HL, and disruption of KIAA0825 on chromosome 5. Given the translocation breakpoints and supporting literature, disruption of ESRRG is the most likely cause for DGAP242's phenotype and implicates ESRRG in a monogenic form of congenital HL, although a putative contributory role for KIAA0825 in the subject's disorder cannot be excluded. European Journal of Human Genetics (2016) 24, 1622-1626; doi:10.1038/ejhg.2016.64; published online 6 July 2016 INTRODUCTIONHearing loss (HL) is one of the most common birth defects, affecting over one in a thousand newborns. Over half of these cases can be attributed to a genetic etiology. 1 Chromosomal abnormalities have been implicated in several genetic forms of congenital HL including Down, Smith-Magenis and Branchio-Oto-Renal syndromes. 2 In cases of congenital HL accompanied with balanced chromosomal abnormalities (BCAs), high resolution of chromosomal breakpoints can reveal genes that have been disrupted, implicating them in auditory pathology. 3 By employing this strategy, the Developmental Genome Anatomy Project (DGAP, dgap.harvard.edu) has successfully resolved the genetic etiology of HL in several cases of BCAs. 4-6 Herein, we report the highresolution breakpoints from a de novo translocation discovered in a 6-year-old female with congenital bilateral sensorineural hearing loss (SNHL) accompanied with a developmental disorder of speech and language.

Age‐related hearing loss: Why we need to think about sex as a biological variable

“…More recently Schilit et al (2016) demonstrated that a translocation between chromosomes 1 and 5 that disrupts the ESRRG gene is strongly implicated as the cause of congenital hearing loss and mild developmental delay in a young female patient (Schilit et al, 2016).…”

Deciphering GRINA/Lifeguard1: Nuclear Location, Ca2+ Homeostasis and Vesicle Transport

“…ESRRG also plays a key role in vascular calcification [117] and is involved in the determination of bone density in women [118]. It crosstalks with ATF6a to coordinate ER stress response [119] and is implicated in hearing loss and mild developmental delays [120]. ESSRG is highly expressed in the nervous system of mice embryos [121], and mice lacking neuronal ESSRG in the cerebral cortex and hippocampus exhibit defects in spatial learning and memory [122].…”

Whole‐genome analysis identifying candidate genes of altitude adaptive ecological thresholds in yak populations

“…Six genes (SH2D5, KIAA0825, LSAMP, KLHL29, PHLDB1 and KNTC1) were not annotated in any known GO term and KEGG functional classification. Most genes, such as KNTC1 (Liu et al, ), PHLDB1 (Baskin et al, ) and SH2D5 (Zheng et al, ), are involved in the development of various tumour cells, neural behaviour (like LSAMP) (Singh et al, ) and sensory ability defects (Schilit et al, ). However, KLHL29 has known functions in the protein degradation process through the ubiquitination pathway, and this gene was also identified as having a heat stress association in catfish (Jin et al, ; Liu et al, ).…”