Somatic mosaicism detected by genome-wide sequencing in 500 parent-child trios with suspected genetic disease: clinical and genetic counseling implications.

Identifying genetic mosaicism is important in establishing a diagnosis, assessing recurrence risk, and providing accurate genetic counseling. Next-generation sequencing has allowed for the identification of mosaicism at levels below those detectable by conventional Sanger sequencing or chromosomal microarray analysis. The CAUSES Clinic was a pediatric translational trio-based genome-wide (exome or genome) sequencing study of 500 families (531 children) with suspected genetic disease at BC Children's and Women's Hospitals. Here we present 12 cases of apparent mosaicism identified in the CAUSES cohort: nine cases of parental mosaicism for a disease-causing variant found in a child and three cases of mosaicism in the proband for a de novo variant. In six of these cases, there was no evidence of mosaicism on Sanger sequencing-the variant was not detected on Sanger sequencing in three cases, and it appeared to be heterozygous in three others. These cases are examples of six clinical manifestations of mosaicism: a proband with classical clinical features of mosaicism (e.g., segmental abnormalities of skin pigmentation or asymmetrical growth of bilateral body parts), a proband with unusually mild manifestations of a disease, a mosaic proband who is clinically indistinguishable from the constitutive phenotype, a mosaic parent with no clinical features of the disease, a mosaic parent with mild manifestations of the disease, and a family in which both parents are unaffected and two siblings have the same disease-causing constitutional mutation. Our data demonstrate the importance of considering the possibility of mosaicism whenever exome or genome sequencing is performed and that its detection via genome-wide sequencing can permit more accurate genetic counseling.

Incidence of septicemia immediately after elective gastrointestinal contrast procedures in infants: a cohort study.

BACKGROUND: Sepsis is a documented complication of gastrointestinal contrast procedures in neonates. However, the identification of preventive measures is hampered by a lack of data on its incidence and risk factors. METHODS: The study used a retrospective cohort analysis of infants with selected surgical gastrointestinal conditions admitted to a tertiary neonatal center. Risk factors were identified by logistic regression and matched case-control analyses. Contrast procedure-related bacteremia or sepsis were defined by clinical signs with or without a positive blood culture, respectively, within 48 hours after an intervention. RESULTS: The apparent incidence of contrast procedure-related sepsis was 2.7 per 100 infant procedures. Infants with contrast procedure-related sepsis were also generally of lower gestational age and birth weight and generally sicker (ie, higher incidence of hepatic cholestatic disease, and poorer weight gain). Notably, all infants with contrast procedure-related sepsis previously had necrotizing enterocolitis. Although the number of cases of sepsis directly attributable to the procedures may be lower, as suggested by a comparison with the baseline time prevalence of bacteremia in this cohort, significant associated morbidities and mortality were observed. CONCLUSIONS: This is the first study reporting the incidence of contrast procedure-related sepsis in high-risk infants with surgical gastrointestinal conditions. Based on our observations, the routine use of prophylactic antibiotics to prevent this complication in this population does not seem warranted.