Work

Heart Transplant for Noncompaction Cardiomyopathy in NONO ‐Related Syndromic Intellectual Disability

Year: 2026

Type: article

Abstract: INTRODUCTION: 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. METHODS: 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". RESULTS: 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. CONCLUSION: 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.

Source: Molecular Genetics & Genomic Medicine

DOI: 10.1002/mgg3.70261

Authors: Julia S. Singer, Dorota Garczarczyk‐Asim, Miriam Michel, Thomas Müller, Lukas Hackl, Andreas R. Janecke

Institutions: Innsbruck Medical University, Universität Innsbruck

Language: English

Topic: Cardiomyopathy and Myosin Studies

Subfield: Cardiology and Cardiovascular Medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,900