title: 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.
authors.affiliation: Department of Genetics, Harvard Medical School, Boston, MA, USA.
authors.forename: Samantha Lp
authors.initials: SL
authors.lastname: Schilit
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women's Hospital, Boston, MA, USA.|Harvard Medical School, Boston, MA, USA.
authors.forename: Benjamin B
authors.initials: BB
authors.lastname: Currall
authors.affiliation: Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Ruen
authors.initials: R
authors.lastname: Yao
authors.affiliation: Molecular Neurogenetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Carrie
authors.initials: C
authors.lastname: Hanscom
authors.affiliation: Molecular Neurogenetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Ryan L
authors.initials: RL
authors.lastname: Collins
authors.affiliation: Molecular Neurogenetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Vamsee
authors.initials: V
authors.lastname: Pillalamarri
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA.
authors.forename: Dong-Young
authors.initials: DY
authors.lastname: Lee
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women's Hospital, Boston, MA, USA.
authors.forename: Tammy
authors.initials: T
authors.lastname: Kammin
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women's Hospital, Boston, MA, USA.|Harvard Medical School, Boston, MA, USA.
authors.forename: Cinthya J
authors.initials: CJ
authors.lastname: Zepeda-Mendoza
authors.affiliation: Department of Clinical Genetics, Kuopio University Hospital, Kuopio, Finland.
authors.forename: Tarja
authors.initials: T
authors.lastname: Mononen
authors.affiliation: UCL Ear Institute, University College London, London, UK.
authors.forename: Lisa S
authors.initials: LS
authors.lastname: Nolan
authors.affiliation: Department of Genetics, Harvard Medical School, Boston, MA, USA.|Harvard Medical School, Boston, MA, USA.|Molecular Neurogenetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA, USA.|Medical and Population Genetics Program, Broad Institute, Cambridge, MA, USA.|Department of Neurology, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: James F
authors.initials: JF
authors.lastname: Gusella
authors.affiliation: Harvard Medical School, Boston, MA, USA.|Molecular Neurogenetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA, USA.|Medical and Population Genetics Program, Broad Institute, Cambridge, MA, USA.|Department of Neurology, Massachusetts General Hospital, Boston, MA, USA.|Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA.|Department of Pathology, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Talkowski
authors.affiliation: Harvard Medical School, Boston, MA, USA.|Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA.|Laboratory for Molecular Medicine, Partners Personalized Medicine, Partners HealthCare, Cambridge, MA, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Shen
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women's Hospital, Boston, MA, USA.|Harvard Medical School, Boston, MA, USA.|Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA.|Medical and Population Genetics Program, Broad Institute, Cambridge, MA, USA.|Manchester Academic Health Science Centre, University of Manchester, Manchester, UK.
authors.forename: Cynthia C
authors.initials: CC
authors.lastname: Morton
mesh_terms: D000328:Adult; D045744:Cell Line, Tumor; D056905:Chromosome Breakpoints; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics; D002658:Developmental Disabilities / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D034381:Hearing Loss / Q000175:diagnosis / Q000235:genetics*; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D010641:Phenotype; D011960:Receptors, Estrogen / Q000235:genetics*; D013577:Syndrome; D014178:Translocation, Genetic
chemical_list: C490917:ESRRG protein, human; D011960:Receptors, Estrogen