ABSTRACT
Kagami-Ogata syndrome is a rare imprinting disorder and its phenotypic overlap with multiple different etiologies hampers diagnosis. Genetic etiologies include paternal uniparental isodisomy (upd(14)pat), maternal allele deletions of differentially methylated regions (DMR) in 14q32.2 or pure primary epimutations. We report a patient with Kagami-Ogata syndrome and an atypical diagnostic odyssey with several negative standard-of-care genetic tests followed by epigenetic testing using methylation microarray and a targeted analysis of whole-genome sequencing to reveal a 203 bp deletion involving the MEG3 transcript and MEG3:TSS-DMR. Long-read sequencing enabled the simultaneous detection of the deletion, phasing, and biallelic hypermethylation of the MEG3:TSS-DMR region in a single assay. This case highlights the challenges in the sequential genetic testing paradigm, the utility of long-read sequencing as a single comprehensive diagnostic assay, and the smallest reported deletion causing Kagami-Ogata syndrome allowing important insights into the mechanism of imprinting effects at this locus.
ABSTRACT
Many children who are HIV infected grow poorly. An epidemiological framework guided a retrospective chart review assessing growth in three groups of children (n = 192): (a) children who were HIV infected secondary to maternal transmission (n = 77), (b) children who had been HIV-positive at birth but became seronegative and continue to be observed (seroreverters) (n = 84), and (c) HIV-infected children who had died (n = 31). Growth failure in the HIV-infected children was significantly greater than that expected in the general population. The seroreverters also demonstrated significantly more growth failure than that expected in the general population. Of the children who had linear growth failure, only 3 of 12 HIV-infected children and 2 of 11 seroreverters also had inadequate weight gain. However, 13 of 15 children with growth failure who subsequently died had poor weight gain. HIV classification was not significantly related to growth. These findings extend our understanding to a large, urban population of children in the United States including those who are older than children in other studies and who developed HIV through perinatal transmission. Nursing clinical practice and research implications are offered.
