Targeted next-generation sequencing identifies the disruption of the SHANK3 and RYR2 genes in a patient carrying a de novo t(1;22)(q43;q13.3) associated with signs of Phelan-McDermid syndrome.
Maria Clara BonagliaSara BertuzzoAnna Maria CiaschiniGiancarlo DiscepoliLucia CastigliaRomina RomanielloOrsetta ZuffardiMarco FicheraPublished in: Molecular cytogenetics (2020)
Although the interruption of SHANK3 accounts for the patient's psychomotor retardation and autism-like behavior, we do not exclude that the interruption of RYR2 may also have a role on her disorder, or result in further pathogenicity in the future. Indeed, RYR2 that has a well-established role in the etiology of two autosomal dominant adulthood cardiac disorders (#600996 and #604772) is also expressed in the brain (cerebellum, hippocampus, and cerebral cortex) and about half of RYR2 mutation carriers present late onset primary generalized epilepsy without cardiac arrhythmogenic disorders. Moreover, RYR2 variants have also been sporadically reported in individuals with early onset schizophrenia or ID, and its constraint values suggest intolerance to loss-of-function. This study not only confirms the usefulness of the molecular mapping of de novo balanced rearrangements in symptomatic individuals, but also underscores the need for long-term clinical evaluation of the patients, for better evaluating the pathogenicity of the chromosomal breakpoints.
Keyphrases
- early onset
- late onset
- case report
- copy number
- genome wide
- left ventricular
- end stage renal disease
- newly diagnosed
- cerebral ischemia
- bipolar disorder
- autism spectrum disorder
- prognostic factors
- biofilm formation
- white matter
- escherichia coli
- mass spectrometry
- depressive symptoms
- dna methylation
- resting state
- functional connectivity
- atrial fibrillation
- current status
- staphylococcus aureus
- patient reported outcomes
- high density
- multiple sclerosis
- circulating tumor cells
- single molecule
- pseudomonas aeruginosa
- cystic fibrosis