Risk of sudden cardiac death in EXOSC5-related disease.
Am J Med Genet A
; 185(8): 2532-2540, 2021 08.
Article
in En
| MEDLINE
| ID: mdl-34089229
ABSTRACT
The RNA exosome is a multi-subunit complex involved in the processing, degradation, and regulated turnover of RNA. Several subunits are linked to Mendelian disorders, including pontocerebellar hypoplasia (EXOSC3, MIM #614678; EXOSC8, MIM #616081 and EXOSC9, MIM #618065) and short stature, hearing loss, retinitis pigmentosa, and distinctive facies (EXOSC2, MIM #617763). More recently, EXOSC5 (MIM *606492) was found to underlie an autosomal recessive neurodevelopmental disorder characterized by developmental delay, hypotonia, cerebellar abnormalities, and dysmorphic facies. An unusual feature of EXOSC5-related disease is the occurrence of complete heart block requiring a pacemaker in a subset of affected individuals. Here, we provide a detailed clinical and molecular characterization of two siblings with microcephaly, developmental delay, cerebellar volume loss, hypomyelination, with cardiac conduction and rhythm abnormalities including sinus node dysfunction, intraventricular conduction delay, atrioventricular block, and ventricular tachycardia (VT) due to compound heterozygous variants in EXOSC5 (1) NM_020158.4c.341C > T (p.Thr114Ile; pathogenic, previously reported) and (2) NM_020158.4c.302C > A (p.Thr101Lys; novel variant). A review of the literature revealed an additional family with biallelic EXOSC5 variants and cardiac conduction abnormalities. These clinical and molecular data provide compelling evidence that cardiac conduction abnormalities and arrhythmias are part of the EXOSC5-related disease spectrum and argue for proactive screening due to potential risk of sudden cardiac death.
Key words
Full text:
1
Database:
MEDLINE
Main subject:
Phenotype
/
RNA-Binding Proteins
/
Death, Sudden, Cardiac
/
Genetic Predisposition to Disease
/
Genetic Association Studies
/
Exosome Multienzyme Ribonuclease Complex
/
Mutation
/
Antigens, Neoplasm
Type of study:
Diagnostic_studies
/
Etiology_studies
/
Prognostic_studies
/
Risk_factors_studies
Limits:
Adult
/
Child
/
Female
/
Humans
/
Male
Language:
En
Journal:
Am J Med Genet A
Journal subject:
GENETICA MEDICA
Year:
2021
Type:
Article
Affiliation country:
United States