title: Reduced L- and M- and increased S-cone functions in an infant with thyroid hormone resistance due to mutations in the THRβ2 gene.
abstract: BACKGROUND
  To document an infant with a cone photoreceptor disorder associated with severe thyroid hormone resistance due to compound heterozygosity in the thyroid hormone receptor beta 2 (TRβ2) encoding gene THRβ2.
  
  
  METHODS
  Cone photoreceptor function was assessed using standard electroretinography (ERG) including colored flashes. We PCR-amplified and sequenced exons 8-10 of the THRβ2 gene. We cloned and sequenced a genomic segment (exons 9-10) of the THRβ2 gene to confirm a compound heterozygote mutation. We investigated whether mutations in the (OPN1LW-OPN1MW) gene array were responsible for the phenotype.
  
  
  RESULTS
  ERG testing showed a normal scotopic response and severely reduced photopic response. Spectral testing showed a small amplitude b-wave to a red flash and a larger amplitude b-wave to the blue flash. Molecular analysis revealed this child was a compound heterozygote for p.R338W and p.R429W mutations in exons 9 and 10 of the THRβ2 gene. These two mutations lie within the ligand-binding domain that is known to selectively inhibit Trβ2 binding as homodimers to the thyroid hormone receptor response elements (TREs). No mutations were found within the OPN1LW and OPN1MW genes or the locus control region that regulates expression of these opsin genes.
  
  
  CONCLUSIONS
  We document a congenital disorder of cone function characterized by severely reduced L- and M-cone responses and increased S-cone responses caused by deleterious mutations in the THRβ2 gene in thyroid resistant patients. Thyroid hormone, via TRβ2, is critical for determining cone-type differentiation in humans.
authors.affiliation: Roger H. Johnson Clinical Vision Laboratory, Division of Ophthalmology, Seattle Children's Hospital, Seattle, WA 98105, USA. avery.weiss@seattlechildrens.org
authors.forename: Avery H
authors.initials: AH
authors.lastname: Weiss
authors.forename: John P
authors.initials: JP
authors.lastname: Kelly
authors.forename: Darren
authors.initials: D
authors.lastname: Bisset
authors.forename: Samir S
authors.initials: SS
authors.lastname: Deeb
mesh_terms: D003117:Color Vision Defects / Q000235:genetics* / Q000378:metabolism; D055358:Cone Opsins / Q000235:genetics / Q000378:metabolism*; D003623:Dark Adaptation; D004596:Electroretinography; D005091:Exons / Q000235:genetics; D005784:Gene Amplification; D006801:Humans; D007223:Infant; D008297:Male; D020417:Nystagmus, Congenital; D010775:Photic Stimulation; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D017949:Retinal Cone Photoreceptor Cells / Q000378:metabolism*; D017299:Rod Opsins / Q000235:genetics / Q000378:metabolism*; D037042:Thyroid Hormone Receptors beta / Q000235:genetics*; D018382:Thyroid Hormone Resistance Syndrome / Q000235:genetics*; D014786:Vision Disorders
chemical_list: D055358:Cone Opsins; D017299:Rod Opsins; D037042:Thyroid Hormone Receptors beta; C095855:long-wavelength opsin; C095854:middle-wavelength opsin