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Phelan–McDermid syndrome (PMS) is a multisystem disorder that is associated with deletions of the 22q13 genomic region or pathogenic variants in the SHANK3 gene. Notable features include developmental issues, absent or delayed speech, neonatal hypotonia, seizures, autism or autistic traits, gastrointestinal problems, renal abnormalities, dolichocephaly, and both macro- and microcephaly. Assessment of the genetic factors that are responsible for abnormal head size in PMS has been hampered by small sample sizes as well as a lack of attention to these features. Therefore, this study was conducted to investigate the relationship between head size and genes on chromosome 22q13. A review of the literature was conducted to identify published cases of 22q13 deletions with information on head size to conduct a pooled association analysis. Across 56 studies, we identified 198 cases of PMS with defined deletion sizes and head size information. A total of 33 subjects (17%) had macrocephaly, 26 (13%) had microcephaly, and 139 (70%) were normocephalic. Individuals with macrocephaly had significantly larger genomic deletions than those with microcephaly or normocephaly (p < 0.0001). A genomic region on 22q13.31 was found to be significantly associated with macrocephaly with CELSR1, GRAMD4, and TBCD122 suggested as candidate genes. Investigation of these genes will aid the understanding of head and brain development. 

Background Higher viral loads in SARS-CoV-2 infections may be linked to more rapid spread of emerging variants of concern (VOC). Rapid detection and isolation of cases with highest viral loads, even in pre- or asymptomatic individuals, is essential for the mitigation of community outbreaks. Methods and findings In this study, we analyze Ct values from 1297 SARS-CoV-2 positive patient saliva samples collected at the Clemson University testing lab in upstate South Carolina. Samples were identified as positive using RT-qPCR, and clade information was determined via whole genome sequencing at nearby commercial labs. We also obtained patient-reported information on symptoms and exposures at the time of testing. The lowest Ct values were observed among those infected with Delta (median: 22.61, IQR: 16.72–28.51), followed by Alpha (23.93, 18.36–28.49), Gamma (24.74, 18.84–30.64), and the more historic clade 20G (25.21, 20.50–29.916). There was a statistically significant difference in Ct value between Delta and all other clades (all p.adj<0.01), as well as between Alpha and 20G (p.adj<0.05). Additionally, pre- or asymptomatic patients (n = 1093) showed the same statistical differences between Delta and all other clades (all p.adj<0.01); however, symptomatic patients (n = 167) did not show any significant differences between clades. Our weekly testing strategy ensures that cases are caught earlier in the infection cycle, often before symptoms are present, reducing this sample size in our population. Conclusions COVID-19 variants Alpha and Delta have substantially higher viral loads in saliva compared to more historic clades. This trend is especially observed in individuals who are pre- or asymptomatic, which provides evidence supporting higher transmissibility and more rapid spread of emerging variants. Understanding the viral load of variants spreading within a community can inform public policy and clinical decision making.