Frontiers in Genetics (Dec 2018)

A NGS-Targeted Autism/ID Panel Reveals Compound Heterozygous GNB5 Variants in a Novel Patient

  • Natascia Malerba,
  • Shelley Towner,
  • Katherine Keating,
  • Gabriella Maria Squeo,
  • William Wilson,
  • Giuseppe Merla

DOI
https://doi.org/10.3389/fgene.2018.00626
Journal volume & issue
Vol. 9

Abstract

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Homozygous and compound heterozygous pathogenic variants in GNB5 have been recently associated with a spectrum of clinical presentations varying from a severe multisystem form of the disorder including intellectual disability, early infantile developmental and epileptic encephalopathy, retinal abnormalities and cardiac arrhythmias (IDDCA) to a milder form with language delay, attention-deficit/hyperactivity disorder, cognitive impairment, with or without cardiac arrhythmia (LADCI). Approximately twenty patients have been described so far; here we report a novel case of a 2.5-year-old female who is a compound heterozygote for a frameshift and a missense variant in the GNB5 gene. Her clinical presentation is consistent with a moderate phenotype, corroborating the direct correlation between the type and pathogenic mechanism of the GNB5 genetic variant and the severity of related phenotype.

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