LMOD2-Related Dilated Cardiomyopathy Presenting in Late Infancy

Authors

Erica Lay
Mahshid S Azamian
Susan W Denfield
William Dreyer
Joseph A Spinner
Debra Kearney
Lilei Zhang
Kim C Worley
Weimin Bi
Seema R Lalani

Publication Date

6-1-2022

Journal

American Journal of Medical Genetics Part A

DOI

10.1002/ajmg.a.62699

PMID

35188328

PMCID

PMC9117498

PubMedCentral® Posted Date

6-1-2022

PubMedCentral® Full Text Version

Author MSS

Published Open-Access

yes

Keywords

Actin Cytoskeleton, Animals, Cardiomyopathies, Cardiomyopathy, Dilated, Cytoskeletal Proteins, Heart, Humans, Infant, Newborn, Mice, Muscle Proteins, Sarcomeres, LMOD2, dilated cardiomyopathy, short thin filament length, autosomal recessive disease, loss of function variant

Abstract

Leiomodin-2 (LMOD2) is an important regulator of the thin filament length, known to promote elongation of actin through polymerization at pointed ends. Mice with Lmod2 deficiency die around 3 weeks of age due to severe dilated cardiomyopathy (DCM), resulting from decreased heart contractility due to shorter thin filaments. To date, there have been three infants from two families reported with biallelic variants in LMOD2, presenting with perinatal onset DCM. Here, we describe a third family with a child harboring a previously described homozygous frameshift variant, c.1243_1244delCT (p.L415Vfs*108) with DCM, presenting later in infancy at 9 months of age. Family history was relevant for a sibling who died suddenly at 1 year of age after being diagnosed with cardiomegaly. LMOD2-related cardiomyopathy is a rare form of inherited cardiomyopathy resulting from thin filament length dysregulation and should be considered in genetic evaluation of newborns and infants with suspected autosomal recessive inheritance or sporadic early onset cardiomyopathy.