Refining critical regions in 15q24 microdeletion syndrome pertaining to autism

Abstract

Chromosome 15q24 microdeletion syndrome is characterized by developmental delay, facial dysmorphism, hearing loss, hypotonia, recurrent infection, and other congenital malformations including microcephaly, scoliosis, joint laxity, digital anomalies, as well as sometimes having autism spectrum disorder (ASD) and attention deficit hyperactivity disorder. Here, we report a boy with a 2.58-Mb de novo deletion at chromosome 15q24. He is diagnosed with ASD and having multiple phenotypes similar to those reported in cases having 15q24 microdeletion syndrome. To delineate the critical genes and region that might be responsible for these phenotypes, we reviewed all previously published cases. We observe a potential minimum critical region of 650 kb (LCR15q24A-B) affecting NEO1 among other genes that might pertinent to individuals with ASD carrying this deletion. In contrast, a previously defined minimum critical region downstream of the 650-kb interval (LCR15q24B-D) is more likely associated with the developmental delay, facial dysmorphism, recurrent infection, and other congenital malformations. As a result, the ASD phenotype in this individual is potentially attributed by genes particularly NEO1 within the newly proposed critical region. K E Y W O R D S15q24 microdeletion, autism spectrum disorder, critical region, de novo

The clinical value of optical genome mapping in the rapid characterization of RB1 duplication and 15q23q24.2 triplication, for more appropriate prenatal genetic counselling

“…Interestingly, the 15q23q24 region contains five low copy repeats (LCRs): LCRs A (BP4), B (BP1), C, D (BP2) and E (BP3) (Liu et al., 2020 ; Mefford et al., 2012 ). The occurrence of several recurrent 15q24 microdeletions (Mefford et al., 2012 ) led to the identification of a new clinically recognizable syndrome defined as Witteveen‐Kolk syndrome (WITKOS; OMIM:613406; ORPHA:94065) and SIN3A as the causative gene.…”

“…The occurrence of several recurrent 15q24 microdeletions (Mefford et al., 2012 ) led to the identification of a new clinically recognizable syndrome defined as Witteveen‐Kolk syndrome (WITKOS; OMIM:613406; ORPHA:94065) and SIN3A as the causative gene. The main reported features are global developmental delay, mild‐to‐moderate intellectual disability, and hypotonia in more than 75% of cases, digital anomalies in 50–75% of cases, and cerebral malformations (including enlarged ventricles) in 25–50% of cases (Liu et al., 2020 ; Magoulas & El‐Hattab, 2012 ; Mefford et al., 2012 ). The majority of deletions are between 1.7 to 6.1 Mb in size, with breakpoints located within the five LCR clusters.…”

Molecular Genetic Analysis of Newborns with Congenital Microcephaly

“…Eleven patients were identified with CNVs in this cohort. Three of the CNVs were associated with chromosome region syndromes, including 22q11 deletion syndrome [21], deletion 3p syndrome [22], and 15q24 microdeletion syndrome [23], of which microcephaly is one of the phenotypes. Two large duplications detected in chr18 and one large duplication detected in chr9 would result in microcephaly [24, 25].…”

Molecular and phenotypic characteristics of 15q24 microdeletion in pediatric patients with developmental disorders

“…ASD was also reported to be an additional phenotype in 15q24 deletion syndrome [ 20 , 21 ]. Recently, a study observed a critical interval of 0.65 Mb in the 15q24 LCR A-B region, which might contribute to ASD [ 22 ]. In our study, case 3, who had a deletion of < 0.57 Mb in the 15q24.1 LCR B-C region, manifested ASD features, including nonverbal communication, social interaction impairment, restricted and repetitive behaviors, hyperactivity, no eye contact, and poor response when called.…”