Heart Transplant for Noncompaction Cardiomyopathy in NONO-Related Syndromic Intellectual Disability.

Authors

Julia S Singer, Dorota Garczarczyk-Asim, Miriam Michel, Thomas Müller, Lukas Hackl, Andreas R Janecke

Published in

Molecular genetics & genomic medicine. Volume 14. Issue 7. Pages e70261.

Abstract

Loss-of-function variants in NONO cause an X-linked syndromic neurodevelopmental disorder (MRXS34), characterized by developmental delay, corpus callosum abnormalities, dysmorphic features, feeding difficulties, and congenital heart disease, most commonly left ventricular noncompaction cardiomyopathy (LVNC). Long-term outcome data remain limited.
A 14-year-old boy with LVNC and syndromic neurodevelopmental features underwent exome sequencing and subsequently NONO transcript analysis. A literature search was conducted using the terms "NONO variant" and "NONO mutation".
Exome sequencing identified a hemizygous NONO variant, c.348G>A, absent from population databases. This silent mutation was predicted in silico to cause exon 4 skipping, resulting in a frameshift and a premature termination codon p.(Asn52Argfs*31). This prediction was confirmed by RT-PCR, and it was demonstrated that the aberrant transcript was subject to nonsense-mediated mRNA decay. The patient displayed the characteristic NONO-associated phenotype with rapid cardiac deterioration requiring pulsatile left ventricular assist device implantation at 1 year of age, and orthotopic heart transplantation at 2 years of age. At 14 years, graft function remains stable. An emergency hemicolectomy due to volvulus was performed at 12 years of age. A literature search identified 32 live-born patients and 11 fetuses with NONO loss-of-function mutations. Intellectual disability, particularly affecting language development, LVNC, a recognizable facial phenotype, dystrophy, and lean habitus were nearly invariantly present.
This report further emphasizes the core phenotype caused by NONO loss-of-function, describes the second individual with heart transplantation, and indicates an underrecognized prevalence of gastrointestinal features.

PMID:
42444102
Bibliographic data and abstract were imported from PubMed on 14 Jul 2026.

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