Recessive ciliopathy mutations in primary endocardial fibroelastosis: a rare neonatal cardiomyopathy in a case of Alstrom syndrome
Journal of Molecular Medicine · 2021
Genomic analysis of an infant with a rare neonatal cardiomyopathy pointed to a ciliopathy gene (ALMS1) as a possible cause.
Research question
What genetic factors may underlie primary endocardial fibroelastosis (pEFE)?
Clinical & scientific significance
To the authors' knowledge, the first evidence linking a ciliopathy (Alström syndrome) to pEFE; infants with pEFE should be examined for syndromic features.
Key findings reported in the paper
- Novel parent-transmitted homozygous variants were found in three cilia-related genes; a frameshift ALMS1 variant (c.1943delA) was prioritized.
- Patient cells showed epithelial-mesenchymal transition and TGFβ activation; ALMS1 loss increased fibroblast migration and cardiomyocyte proliferation.
Objectives
To investigate genetic contributors to pEFE using integrated genomics in a pathologically confirmed case.
Methods
Whole-exome sequencing and RNA-seq in a female infant, with functional studies in patient fibroblasts, neonatal cardiac fibroblasts and cardiomyocytes.
This summary is based only on the published abstract.
Finding a genetic cause in a single infant
01
Rare diagnosis
An infant with pathologically confirmed primary endocardial fibroelastosis.
02
Exome sequencing
Reading the protein-coding genes to look for inherited variants.
03
RNA sequencing
Measuring which genes are switched on in the patient's cells.
04
Candidate variant
A change in ALMS1, a gene linked to cilia, was prioritized.
05
Functional testing
Cell experiments showed altered signaling, migration and proliferation.
Read the publication
Authors
Zhao Y, Wang LK, Eskin A, Kang X, Fajardo VM, Mehta Z, Pineles S, Schmidt RJ, Nagiel A, Satou G, Garg M, Federman M, Reardon LC, Lee SL, Biniwale R, Grody WW, Halnon N, Khanlou N, Quintero-Rivera F, Alejos JC, Nakano A, Fishbein GA, Van Arsdell GS, Nelson SF, Touma M
Citation
Recessive ciliopathy mutations in primary endocardial fibroelastosis: a rare neonatal cardiomyopathy in a case of Alstrom syndrome. J Mol Med (Berl). 2021; 99(11):1623-1638. doi:10.1007/s00109-021-02112-z. PMID: 34387706.
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