Biallelic TMEM260 variants cause truncus arteriosus, with or without renal defects.
Clin Genet
; 101(1): 127-133, 2022 01.
Article
in En
| MEDLINE
| ID: mdl-34612517
ABSTRACT
Only two families have been reported with biallelic TMEM260 variants segregating with structural heart defects and renal anomalies syndrome (SHDRA). With a combination of genome, exome sequencing and RNA studies, we identified eight individuals from five families with biallelic TMEM260 variants. Variants included one multi-exon deletion, four nonsense/frameshifts, two splicing changes and one missense change. Together with the published cases, analysis of clinical data revealed ventricular septal defects (12/12), mostly secondary to truncus arteriosus (10/12), elevated creatinine levels (6/12), horse-shoe kidneys (1/12) and renal cysts (1/12) in patients. Three pregnancies were terminated on detection of severe congenital anomalies. Six patients died between the ages of 6 weeks and 5 years. Using a range of stringencies, carrier frequency for SHDRA was estimated at 0.0007-0.007 across ancestries. In conclusion, this study confirms the genetic basis of SHDRA, expands its known mutational spectrum and clarifies its clinical features. We demonstrate that SHDRA is a severe condition associated with substantial mortality in early childhood and characterised by congenital cardiac malformations with a variable renal phenotype.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Truncus Arteriosus
/
Alleles
/
Heart Defects, Congenital
/
Kidney Diseases
/
Membrane Proteins
Type of study:
Diagnostic_studies
/
Prognostic_studies
Limits:
Humans
Language:
En
Journal:
Clin Genet
Year:
2022
Document type:
Article
Affiliation country: