The Impact of Asymptomatic Congenital Cytomegalovirus on Adult Quality of Life.

OBJECTIVE: Children born with asymptomatic congenital cytomegalovirus infection (AcCMV) have increased risk for hearing loss, which may affect their quality of life into adulthood. We aim to determine quality of life outcomes among adults who were identified at birth with AcCMV compared with controls, using the cohort of the Houston Congenital CMV Longitudinal Study. METHODS: Quality of life was determined using the self-reported Quality of Life Inventory (QOLI). Sixty-one of 109 AcCMV subjects and 23 of 51 controls completed QOLI. Percentile scores of subjects were compared with percentile scores of controls using Student t tests. QOLI percentile scores were compared among AcCMV subjects with (N = 14) and without hearing loss (N = 47). RESULTS: There was no difference in mean percentile scores on QOLI between AcCMV subjects (59.8 [SD = 27.6]) and controls (57.3 [SD = 35.3]; p = 0.754). Percentile scores indicate an average overall quality of life classification for AcCMV subjects and controls. There was no difference in mean percentile scores on the QOLI between AcCMV subjects with and without hearing loss (54.8 [SD = 25.2]) and 61.3 [SD = 28.3]; p = 0.440, respectively). CONCLUSION: Adults born with AcCMV do not seem to have lower ratings of quality of life compared with uninfected controls. Although our study had small sample size, hearing loss does not seem to be a significant predictor of QOLI percentile scores among AcCMV subjects. Quality of life in adulthood does not seem to be affected by an individual's awareness of screening positive for CMV, which supports the notion of "no harm" occurring from universal newborn screening for congenital CMV infection.

ZMIZ1 Variants Cause a Syndromic Neurodevelopmental Disorder.

ZMIZ1 is a coactivator of several transcription factors, including p53, the androgen receptor, and NOTCH1. Here, we report 19 subjects with intellectual disability and developmental delay carrying variants in ZMIZ1. The associated features include growth failure, feeding difficulties, microcephaly, facial dysmorphism, and various other congenital malformations. Of these 19, 14 unrelated subjects carried de novo heterozygous single-nucleotide variants (SNVs) or single-base insertions/deletions, 3 siblings harbored a heterozygous single-base insertion, and 2 subjects had a balanced translocation disrupting ZMIZ1 or involving a regulatory region of ZMIZ1. In total, we identified 13 point mutations that affect key protein regions, including a SUMO acceptor site, a central disordered alanine-rich motif, a proline-rich domain, and a transactivation domain. All identified variants were absent from all available exome and genome databases. In vitro, ZMIZ1 showed impaired coactivation of the androgen receptor. In vivo, overexpression of ZMIZ1 mutant alleles in developing mouse brains using in utero electroporation resulted in abnormal pyramidal neuron morphology, polarization, and positioning, underscoring the importance of ZMIZ1 in neural development and supporting mutations in ZMIZ1 as the cause of a rare neurodevelopmental syndrome.