Maternally inherited deletion encompassing the RTL1as and MEG8 genes of the human 14q32 imprinted region in a patient with a mild Kagami‐Ogata syndrome phenotype

Abstract

Kagami-Ogata syndrome and Temple syndrome are imprinting disorders caused by the abnormal expression of genes in an imprinted cluster on chromosome 14q32.Here, we report a female with mild features of the Kagami-Ogata syndrome phenotype with polyhydramnios, neonatal hypotonia, feeding difficulties, abnormal foot morphology, patent foramen ovale, distal arthrogryposis, normal facial profile, and a bell-shaped thorax without coat hanger ribs. The single nucleotide polymorphism array revealed the interstitial deletion of chromosome 14q32.2-q32.31 (117 kb in size), involving the RTL1as and MEG8 genes, and other small nucleolar RNAs and microRNAs. The differentially methylated regions (DMRs) appeared unaltered. The RTL1as gene deletion and the normal methylation pattern of the MEG3 gene loci were confirmed by methylation-specific multiplex ligation-dependent probe amplification. Deletions of the 14q32 region without involving DMRs, and encompassing only the RTL1as and MEG8 genes, are poorly described in the literature. The mother's chromosomal microarray also confirmed the identical 14q32.2 deletion, although she presented a normal phenotype. The maternally inherited 14q32 deletion was responsible for Kagami-Ogata syndrome in our patient.

Imprinted small nucleolar RNAs: Missing link in development and disease?

“…The most important question is whether microdeletions involving only microRNA and snoRNA clusters, not DMRs or the MEG3 gene, can lead to KOS14 phenotypes. A recent report provides some insights concerning an individual with deletion of 117 kb (14q32.2-q32.31) encompassing miRNA and snoRNA clusters who developed mild features of KOS14 such as polyhydramnios, neonatal hypotonia, and a bell-shaped thorax but not coat-hanger ribs (Sirera Sirera et al, 2023).…”