MYL9 – Visceral Myopathy 1

In a recent case report, biallelic loss‑of‑function variants in MYL9 were identified in patients presenting with features of visceral myopathy 1, a severe form of megacystis‐microcolon‐intestinal hypoperistalsis syndrome. The proband exhibited hallmark symptoms including megacystis (HP:0000021) and intestinal pseudo‑obstruction (HP:0004389). Genetic testing revealed compound heterozygous alterations, one being a nine base pair deletion that disrupts the canonical splice donor site (c.184+2_184+10del) and a second deleterious event, with parental testing confirming in trans configuration (PMID:33031641). In addition, a previously reported case documented a homozygous deletion in the same gene, thereby reinforcing the association even though the total number of probands remains limited.

Functional investigations in related studies have demonstrated that MYL9 plays a key role in myosin regulatory mechanisms that impact smooth muscle contractility. Although experimental data from cellular models such as HeLa cells suggest that altered MYL9 expression may affect cytoplasmic contractility, direct functional studies in visceral smooth muscle tissue are currently lacking (PMID:26663899). Together, these findings support a limited yet clinically relevant gene-disease association for MYL9 in visceral myopathy 1, warranting its inclusion in diagnostic genetic testing panels for MMIHS and related smooth muscle disorders. This emerging evidence, while not yet extensive, provides a critical basis for enhancing diagnostic decision‑making and guiding future research.

References

• Molecular Genetics & Genomic Medicine • 2020 • Compound heterozygous loss of function variants in MYL9 in a child with megacystis-microcolon-intestinal hypoperistalsis syndrome PMID:33031641
• Cytoskeleton (Hoboken, N.J.) • 2015 • Characterization of myosin II regulatory light chain isoforms in HeLa cells PMID:26663899

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