title: Expanding the Phenotype of TRNT1-Related Immunodeficiency to Include Childhood Cataract and Inner Retinal Dysfunction.
abstract: OBJECTIVE
  A multiorgan syndromic disorder characterized by sideroblastic anemia, immunodeficiency, periodic fever, and developmental delay with an uncharacterized retinal dystrophy is caused by TRNT1. This report of a family with a homozygous mutation in TRNT1 expands the ocular phenotype to include cataract and inner retinal dysfunction and details a mild systemic phenotype.
  
  
  METHODS
  A consanguineous family with 3 affected children was investigated. Key clinical features comprised hypogammaglobulinemia, short stature with microcephaly, cataract, and inner retinal dysfunction without sideroblastic anemia or developmental delay. Two siblings had poor balance and 1 sibling had sensorineural hearing loss. The oldest sibling had primary ovarian failure diagnosed at age 14.5 years. Exome sequencing identified a homozygous missense variant in TRNT1, c.295C>T (p.Arg99Trp) in all 3 patients. The sibling with hearing loss also harbored a homozygous mutation in GJB2, c.71G>A (p.Trp24*), which is an established cause of sensorineural hearing loss.
  
  
  CONCLUSIONS
  This family expands the ocular and systemic phenotypes associated with mutations in TRNT1, demonstrating phenotypic variability and highlighting the need for ophthalmic review of these patients.
authors.affiliation: Institute of Ophthalmology, University College London, London, England2Moorfields Eye Hospital, London, England.
authors.forename: Sarah
authors.initials: S
authors.lastname: Hull
authors.affiliation: Moorfields Eye Hospital, London, England.
authors.forename: Aeesha N J
authors.initials: AN
authors.lastname: Malik
authors.affiliation: Institute of Ophthalmology, University College London, London, England2Moorfields Eye Hospital, London, England.
authors.forename: Gavin
authors.initials: G
authors.lastname: Arno
authors.affiliation: Department of Ophthalmology and Visual Sciences, Washington University in St Louis, St Louis, Missouri.
authors.forename: Donna S
authors.initials: DS
authors.lastname: Mackay
authors.affiliation: Genetics Institute, University College London, London, England.
authors.forename: Vincent
authors.initials: V
authors.lastname: Plagnol
authors.affiliation: Institute of Ophthalmology, University College London, London, England2Moorfields Eye Hospital, London, England.
authors.forename: Michel
authors.initials: M
authors.lastname: Michaelides
authors.affiliation: Medical Genetics Unit, St George's University of London, London, England.
authors.forename: Sahar
authors.initials: S
authors.lastname: Mansour
authors.affiliation: Paediatric Infectious Diseases Unit, St George's Hospital, London, England.
authors.forename: Assunta
authors.initials: A
authors.lastname: Albanese
authors.affiliation: Medical Genetics Unit, St George's University of London, London, England.
authors.forename: Katrina Tatton
authors.initials: KT
authors.lastname: Brown
authors.affiliation: Institute of Ophthalmology, University College London, London, England2Moorfields Eye Hospital, London, England.
authors.forename: Graham E
authors.initials: GE
authors.lastname: Holder
authors.affiliation: Institute of Ophthalmology, University College London, London, England2Moorfields Eye Hospital, London, England.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Webster
authors.affiliation: Paediatric Infectious Diseases Unit, St George's Hospital, London, England.
authors.forename: Paul T
authors.initials: PT
authors.lastname: Heath
authors.affiliation: Institute of Ophthalmology, University College London, London, England2Moorfields Eye Hospital, London, England7Department of Ophthalmology, University of California, San Francisco.
authors.forename: Anthony T
authors.initials: AT
authors.lastname: Moore
mesh_terms: D000293:Adolescent; D002386:Cataract / Q000150:complications* / Q000235:genetics / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D059472:Exome; D005260:Female; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000150:complications* / Q000235:genetics / Q000378:metabolism; D007223:Infant; D008297:Male; D009154:Mutation; D009713:Nucleotidyltransferases / Q000235:genetics* / Q000378:metabolism; D010375:Pedigree; D010641:Phenotype; D058499:Retinal Dystrophies / Q000150:complications* / Q000235:genetics / Q000378:metabolism; D017422:Sequence Analysis, DNA
chemical_list: D009713:Nucleotidyltransferases; C000610948:TRNT1 protein, human