Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0018799 (
heart disease
)
34,133
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Congenital heart disease (CHD) associated with polydactyly involves various genes. We aimed to identify variations from genes related to complex CHD with polydactyly and to investigate the cellular functions related to the mutations. Blood was collected from a complex CHD case with polydactyly, and whole exome sequencing (WES) was performed. The CRISPR/Cas9 system was used to generate human pluripotent stem cell with mutations (hPSCs-Mut) that were differentiated into cardiomyocytes (hPSC-CMs-Mut) and analysed by transcriptomics on day 0, 9 and 13. Two heterozygous mutations, LTBP2 (c.2206G>A, p.Asp736Asn, RefSeq NM_000428.2) and
TCTN3
(c.1268G>A, p.Gly423Glu, RefSeq NM_015631.5), were identified via WES but no TBX5 mutations were found. The stable cell lines of hPSCs-LTBP2
mu
/
TCTN3
mu
were constructed and differentiated into hPSC-CMs-LTBP2
mu
/
TCTN3
mu
. Compared to the wild type, LTBP2 mutation delayed the development of CMs. The
TCTN3
mutation consistently presented lower rate and weaker force of the contraction of CMs. For gene expression pattern of persistent up-regulation, pathways in cardiac development and congenital
heart disease
were enriched in hPSCs-CM-LTBP2
mu
, compared with hPSCs-CM-WT. Thus, the heterozygous mutations in
TCTN3
and LTBP2 affect contractility (rate and force) of cardiac myocytes and may affect the development of the heart. These findings provide new insights into the pathogenesis of complex CHD with polydactyly.
...
PMID:Novel mutations of TCTN3/LTBP2 with cellular function changes in congenital heart disease associated with polydactyly. 3309 76
