Biallelic TMEM260 variants cause truncus arteriosus, with or without renal defects

Genomics England Research Consortium, Alistair T. Pagnamenta, Adam Jackson, Rahat Perveen, Glenda Beaman, Gemma Petts, Asheeta Gupta, Zerin Hyder, Brian Hon Yin Chung, Anita Sik Yau Kan, Ka Wang Cheung, Wilhelmina S. Kerstjens-Frederikse, Kristin M. Abbott, Orly Elpeleg, Jenny C. Taylor, Siddharth Banka*, Asaf Ta-Shma

*Corresponding author for this work

    Research output: Contribution to journalArticleAcademicpeer-review

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    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.

    Original languageEnglish
    Pages (from-to)127-133
    Number of pages7
    JournalClinical Genetics
    Issue number1
    Publication statusPublished - Jan-2022


    • exome sequencing
    • genome sequencing
    • kidney
    • phenotypic variability
    • renal failure
    • SHDRA
    • structural heart defects and renal anomalies syndrome
    • TMEM260
    • truncus arteriosus

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