Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2022 Jun;114(10):499-504.
doi: 10.1002/bdr2.2011. Epub 2022 Apr 15.

Biallelic THOC6 pathogenic variants: Prenatal phenotype and review of the literature

Lyse Ruaud  1   2 , Nathalie Roux  3   4 , Lucile Boutaud  3   5 , Bettina Bessières  3 , Faustine Ageorges  2 , Amale Achaiaa  3 , Christine Bole  6 , Patrick Nitschke  4   6 , Cécile Masson  6 , Michel Vekemans  3   4   5 , Alain Verloes  1   2 , Tania Attie-Bitach  3   4   5
Affiliations
Review

Biallelic THOC6 pathogenic variants: Prenatal phenotype and review of the literature

Lyse Ruaud et al. Birth Defects Res. 2022 Jun.

Abstract

Background: The THOC6 protein is a component of the THO complex. It is involved in mRNA transcription, processing and nuclear export. Interestingly molecular biallelic loss-of-function variants of the THOC6 gene were identified in the Beaulieu-Boycott-Innes syndrome (BBIS- OMIM # 613680). This condition was described in 17 patients and is characterized by a moderate to severe intellectual disability, facial dysmorphic features and severe birth defects such as heart, skeletal, ano-genital and renal congenital malformations.

Methods: In the present study, we report on a new family with two affected sibs. The 6-year-old female had severe intellectual disability with autistic features, feeding difficulties, growth delay, facial dysmorphic, and congenital malformations (hand, skeletal and cardiac anomalies). The male fetus presented antenatally with a cystic hygroma associated with severe aortic and left ventricular hypoplasia. Autopsy, after termination of pregnancy at 15 weeks of gestation, showed facial dysmorphic, short right thumb and hypospadias.

Results: Exome sequencing detected in both sibs compound heterozygous variants of the THOC6 gene (NM_024339.3, GRCh37): the already reported c.[298T>A;700G>T;824G>A] haplotype and a novel variant c.977T>G, p.(Val326Gly).

Discussion: We made a review of the literature of 17 BBIS reported patients including our two siblings. Severe to moderate ID and congenital malformations were constant. Prenatal and postnatal failure to thrive were frequent. Brain MRI were not specific. Prenatal findings were reported in 40% of cases but we described the first case of cystic hygroma. The present study reports extends the prenatal delineation of the phenotypic features observed in association with the presence of THOC6 variants. In addition, it underscores the intrafamilial phenotypic variability observed in BBIS.

Keywords: Beaulieu-Boycott-Innes syndrome; THOC6 gene; prenatal phenotype.

PubMed Disclaimer

References

REFERENCES

    1. Accogli, A., Scala, M., Calcagno, A., Castello, R., Torella, A., Musacchia, F., … Capra, V. (2018). Novel CNS malformations and skeletal anomalies in a patient with Beaulieu-Boycott-Innes syndrome. American Journal of Medical Genetics. Part A, 176(12), 2835-2840. https://doi.org/10.1002/ajmg.a.40534
    1. Amos, J. S., Huang, L., Thevenon, J., Kariminedjad, A., Beaulieu, C. L., Masurel-Paulet, A., … Care4Rare Canada Consortium. (2017). Autosomal recessive mutations in THOC6 cause intellectual disability: Syndrome delineation requiring forward and reverse phenotyping. Clinical Genetics, 91(1), 92-99. https://doi.org/10.1111/cge.12793
    1. Anazi, S., Alshammari, M., Moneis, D., Abouelhoda, M., Ibrahim, N., & Alkuraya, F. S. (2016). Confirming the candidacy of THOC6 in the etiology of intellectual disability. American Journal of Medical Genetics. Part A, 170A(5), 1367-1369. https://doi.org/10.1002/ajmg.a.37549
    1. Beaulieu, C. L., Huang, L., Innes, A. M., Akimenko, M.-A., Puffenberger, E. G., Schwartz, C., … Boycott, K. M. (2013). Intellectual disability associated with a homozygous missense mutation in THOC6. Orphanet Journal of Rare Diseases, 8, 62. https://doi.org/10.1186/1750-1172-8-62
    1. Boycott, K. M., Beaulieu, C., Puffenberger, E. G., McLeod, D. R., Parboosingh, J. S., & Innes, A. M. (2010). A novel autosomal recessive malformation syndrome associated with developmental delay and distinctive facies maps to 16ptel in the Hutterite population. American Journal of Medical Genetics. Part A, 152A(6), 1349-1356. https://doi.org/10.1002/ajmg.a.33379

LinkOut - more resources