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

Figures

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  FIGURE 1. Subcostal long‐axis echocardiographic view demonstrating marked dilation of the left atrium (LA) and left ventricle (LV) with prominent LV trabeculations and deep intertrabecular recesses consistent with extensive LV noncompaction at 1 year of age. RA—right atrium.

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  FIGURE 2. Shared facial gestalt in patients with NONO loss‐of‐function variants. (A) Patient reported here at age 14 years. (B–S) Patients reported in references (Carlston et al. 2019; Coetzer and Moosa 2022; Mircsof et al. 2015; Planté‐Bordeneuve et al. 2025; Reinstein et al. 2016; Roessler et al. 2023; Sewani et al. 2020; Xi et al. 2024).

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  FIGURE 3. (A) Detection of a NONO (NM_007363.5), c.348G>A variant by Sanger sequencing, hemizygous in the proband and heterozygous in his mother as compared to control (wild‐type). (B) PCR amplification of exons 3 to 5 of NONO cDNA demonstrates two aberrant bands (indicated by a red arrow and a yellow arrow) in the patient in addition to the wild‐type band (indicated by a blue arrow) by agarose gel electrophoresis, as compared to controls. The aberrant band of lower molecular weight (red arrow) is sensitive to NMD, as high amounts are amplified in cDNA from puromycin‐treated cells (+p), as compared to cDNA from untreated cells (−p). In cells with inhibited protein synthesis, this aberrant band represents the major NONO transcript in the patient. The additional band of higher molecular weight in the patient might represent another abnormal splicing product, not sensitive to NMD, being present in minor amounts and was thus not subjected to sequencing. (C) Sanger sequencing of this aberrant band (red arrow) demonstrates exon 4 skipping, with deletion of 194 bp of the open reading frame; Sanger sequencing of the prevalent band in controls demonstrates the full‐length transcript NM_007363.5…

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  FIGURE 4. Schematic representation of the structure of NONO with 12 exons and a compilation of reported pathogenic NONO variants in 33 live‐born patients and in 11 fetuses.