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Alternative estrogen receptor β promoter utilization causes mild intellectual disability

Tuesday, October 25, 2011 — Poster Session II

Noon – 2:00 p.m.

Natcher Conference Center




  • N Tarazi
  • V Maduro
  • R Wersto
  • J Mullikin
  • R Legaspi
  • NISC Comparative Sequencing Program
  • W Gahl
  • C Boerkoel


Intellectual disability has a prevalence of 1-3%. However, despite the high prevalence and morbidity, its physiologic bases remain poorly understood. Estrogen is a neuroprotective agent in the prevention and/or amelioration of some neurologic and mental disorders, including cognitive and memory dysfunctions, brain injury and stroke, and neurodegenerative diseases. We present a family segregating a mutation of the estrogen receptor beta (ERβ) gene. The grandmother had a mild intellectual disability (0.1 percentile) as well as verbal and visual memory impairments. Her 31-year-old son was within the mild intellectual disability range (0.2 percentile), with nonverbal reasoning significantly lower than verbal reasoning. Her four-year-old grandson had speech and language delay with overall intellectual (8th percentile) and adaptive functioning (4th percentile) in the low average range. Chromosome analysis and sequencing identified a translocation disrupting the ERβ promoter; by RT-PCR we show that this changes transcript abundance originating from the ERβ promoters. Additionally, by RT-PCR profiling of ERβ promoter utilization in different tissues, we provide an hypothesis for the mechanism of this family’s cognitive problems. This description of a human ERβ mutation validates the behavioral phenotype observed in the ERβ knockout mice as a model of human disease.

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