First report of two successive deletions on chromosome 15q13 cytogenetic bands in a boy and girl: additional data to 15q13.3 syndrome with a report of high IQ patient

Abstract

15q13.3 syndrome is associated with a wide spectrum of neurological disorders. Among a cohort of 150 neurodevelopmental cases, we identified two patients with two close proximity interstitial hemizygous deletions on chromosome 15q13. Using high-density microarrays, we characterized these deletions and their approximate breakpoints. The second deletion in both patients overlaps in a small area containing CHRNA7 where the gene is partially deleted. The CHRNA7 is considered a strong candidate for the 15q13.3 deletion syndrome’s pathogenicity. Patient 1 has cognitive impairment, learning disabilities, hyperactivity and subtle dysmorphic features whereas patient 2 has mild language impairment with speech difficulty, mild dysmorphia, heart defect and interestingly a high IQ that has not been reported in 15q13.3 syndrome patients before. Our study presents first report of such two successive deletions in 15q13.3 syndrome patients and a high IQ in a 15q13.3 syndrome patient. Our study expands the breakpoints and phenotypic features related to 15q13.3 syndrome.

Yield of array‐CGH analysis in Tunisian children with autism spectrum disorder

“…In addition to its ionotropic neuronal functions, modulating the secretion of both the inhibitory neurotransmitter GABA and the excitatory neurotransmitter glutamate, the α7 nicotinic receptor is also able to regulate neuroinflammation through independent metabotropic effects detected in many nonneuronal cell types (Papke & Lindstrom, 2020 ; Zoli et al, 2018 ). The differential burden of OTUD7A and CHRNA7 is well exemplified by a recent report describing a boy and a girl, each carrying two contiguous 15q13.3 microdeletions involving CHRNA7 and displaying very different clinical phenotypes: the boy has severe cognitive impairment and hyperactivity, while the girl had mild language deficits and a high IQ (Alsagob et al, 2019 ). Interestingly, the downstream deletion includes both OTUD7A and CHRNA7 in the severely affected boy, while only CHRNA7 is deleted in the mildly affected girl (Alsagob et al, 2019 ).…”

“…The differential burden of OTUD7A and CHRNA7 is well exemplified by a recent report describing a boy and a girl, each carrying two contiguous 15q13.3 microdeletions involving CHRNA7 and displaying very different clinical phenotypes: the boy has severe cognitive impairment and hyperactivity, while the girl had mild language deficits and a high IQ (Alsagob et al, 2019). Interestingly, the downstream deletion includes both OTUD7A and CHRNA7 in the severely affected boy, while only CHRNA7 is deleted in the mildly affected girl (Alsagob et al, 2019). In line with this evidence, our case n. 23 carries a deletion involving both genes and is severely affected with ASD, cognitive impairment and lack of verbal language. Chr.…”

Mice with mutations in Trpm1, a gene within the locus of 15q13.3 microdeletion syndrome, display pronounced hyperactivity and decreased anxiety-like behavior.

“…Hyperactivity is one of the features of ADHD, and a patient with 15q13.3 deletion, who had a relative lack of expression of genes including TRPM1, showed ADHD behavior [30][31][32][33][34][35][36][37]. We examined the effect of MPH, which is often used as a rst choice for treatment of ADHD in humans [26], however, MPH signi cantly increased the locomotion activity of Trpm1 −/− mice (Fig.…”

Mice with Mutations in Trpm1, a Gene within the locus of 15q13.3 Microdeletion Syndrome, Display Pronounced Hyperactivity and Decreased Anxiety-Like Behavior.

“…1-3). Hyperactivity is one of the features of ADHD, and a patient with 15q13.3 deletion, who had a relative lack of expression of genes including TRPM1, showed ADHD behavior [36][37][38][39][40][41][42][43]. We examined the effect of MPH which is often used for treatment of ADHD, however, MPH signi cantly increase the locomotion activity of Trpm1 −/− mice (Fig.…”