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387 ANGELMAN SYNDROME: A NOVEL UBE3A MUTATION AND A UNIQUE VARIANT PHENOTYPE.
  1. E. Johnson
  1. Primary Children's Medical Center, Salt Lake City, UT

Abstract

Angelman syndrome (AS) is an inherited neurodevelopmental disorder that is clinically characterized by severe speech impairment, unusually happy demeanor, ataxia, microcephaly, and EEG abrnomalities. Functional deficits of the UBE3A gene in the 15q11-13 region of the maternal chromosome lead to the Angelman syndrome phenotype. Genetic analysis has revealed four mechanisms that are known to cause Angelman syndrome. They have been grouped in classes I though IV. Class I defects account for 70% of AS patients and result from a deletion in chromosome 15q11-13. Class II defects are less common and are the result of uniparental disomy. Class III patients have imprinting defects of 15q11-13. Class IV patients account for 20% of AS and have mutations in the UBE3A gene. The type of deletion has been linked to phenotypic severity and class I patients generally have the most severe phenotypes. We have been following a 10-year-old boy with a novel UBE3A mutation and a normal methylation pattern. His mutation is a G—> A substitution at position 1434 in exon 9 of UBE3A. He has some classical Angelman features, including a wide mouth, flat face, happy demeanor, severe speech impairment, and sleep disturbance. However, he is not microcephalic, has no EEG abnormalities, and is not ataxic. This patient's presentation presented a diagnostic challenge because he lacks multiple “classical” Angelman characteristics. We hypothesize that this novel UBE3A mutation produced a unique variant phenotype and provides further knowledge to genotype-phenotype relationships within the Angelman syndrome spectrum.

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