A novel heterozygous ZBTB18 missense mutation in a family with non-syndromic intellectual disability.

Intellectual disability (ID) is a common neurodevelopmental disorder characterized by significantly impaired adaptive behavior and cognitive capacity. High throughput sequencing approaches have revealed the genetic etiologies for 25-50% of ID patients, while inherited genetic mutations were detected in <5% cases. Here, we investigated the genetic cause for non-syndromic ID in a Han Chinese family. Whole genome sequencing was performed on identical twin sisters diagnosed with ID, their respective children, and their asymptomatic parents. Data was filtered for rare variants, and in silico prediction tools were used to establish pathogenic alleles. Candidate mutations were validated by Sanger sequencing. In silico modeling was used to evaluate the mutation's effects on the protein encoded by a candidate coding gene. A novel heterozygous variant in the ZBTB18 gene c.1323C>G (p.His441Gln) was identified. This variant co-segregated with affected individuals in an autosomal dominant pattern and was not detected in asymptomatic family members. Molecular studies reveal that a p.His441Gln substitution disrupts zinc binding within the second zinc finger and disrupts the capacity for ZBTB18 to bind DNA. This is the first report of an inherited ZBTB18 mutation for ID. This study further validates WGS for the accurate molecular diagnosis of ID.

Neonatal mortality and leading causes of deaths: a descriptive study in China, 2014-2018.

OBJECTIVE: The present study estimated the national and urban-rural levels and causes of neonatal deaths in China annually between 2014 and 2018 to provide data support for the further end of preventable neonatal deaths for China and other low-income and middle-income countries. METHODS: The study was based on data from the National Maternal and Child Health Surveillance System. All neonates of surveillance districts (gestational week: ≥28 weeks) who died after delivery have been involved in the study. The mortality rate and the leading causes of death for neonates were analysed. RESULTS: The neonatal mortality rate (NMR) of China has steadily decreased from 5.9 deaths per 1000 live births in 2014 to 3.9 deaths per 1000 live births in 2018. The NMR in 2018 of urban and rural areas was 2.2 deaths per 1000 live births and 4.7 deaths per 1000 live births, respectively. The leading preventable causes of neonatal deaths are the same in the urban and rural areas were same, which were preterm birth, intrapartum complications and pneumonia. Mortality rates of these three causes fell significantly between 2014 and 2018 but contributed to a higher proportion of deaths in rural areas than urban areas. The proportion of preventable deaths accounted for 74.6% in 2018. CONCLUSIONS: The NMR of China has decreased steadily from 2014 to 2018. However, the inequality between urban and rural areas still exists. The goal of government interventions should be to reduce the health inequality of neonates and further take targeted measures to eliminate preventable neonatal death.