A novel homozygous mutation in TRAPPC9 gene causing autosomal recessive non-syndromic intellectual disability

Mutaz Amin; Cedric Vignal; Esraa Eltaraifee; Inaam N Mohammed; Ahlam A A Hamed; Maha A Elseed; Arwa Babai; Iman Elbadi; Doua Mustafa; Rayan Abubaker; Mohamed Mustafa; Severine Drunat; Liena E O Elsayed; Ammar E Ahmed; Odile Boespflug-Tanguy; Imen Dorboz

doi:10.1186/s12920-022-01354-1

A novel homozygous mutation in TRAPPC9 gene causing autosomal recessive non-syndromic intellectual disability

BMC Med Genomics. 2022 Nov 8;15(1):236. doi: 10.1186/s12920-022-01354-1.

Authors

Mutaz Amin^{1

2}, Cedric Vignal³, Esraa Eltaraifee⁴, Inaam N Mohammed⁴, Ahlam A A Hamed⁴, Maha A Elseed⁴, Arwa Babai⁴, Iman Elbadi⁴, Doua Mustafa⁴, Rayan Abubaker^{4

5}, Mohamed Mustafa⁴, Severine Drunat^{2

3}, Liena E O Elsayed⁶, Ammar E Ahmed⁴, Odile Boespflug-Tanguy^{2

7}, Imen Dorboz^{8

9}

Affiliations

¹ Faculty of Medicine, Al-Neelain University, Khartoum, Sudan.
² INSERM UMR 1141 PROTECT, Université Paris Diderot- Sorbonne Paris Cité, Paris, France.
³ Unité de Génétique Moleculaire, Departement de Genetique Médicale, APHP, Hopital Robert-Debré, 75019, Paris, France.
⁴ Faculty of Medicine, University of Khartoum, Khartoum, Sudan.
⁵ National University Biomedical Research Institute, National University, Khartoum, Sudan.
⁶ Department of Basic Sciences, College of Medicine, Princess Nourah Bint Abdulrahman University, P.O. Box 84428, Riyadh, 11671, Saudi Arabia.
⁷ Neuropediatrics and Metabolic Disorders Department, Reference Center for Leukodystrophies and Rare Leukoencéphalopathies (LEUKOFRANCE), CHU APHP Robert-Debré, Imen DORBOZ: INSERM U1141, Hopital Robert Debre, 48 boulevard Serurier, 75019, Paris, France.
⁸ INSERM UMR 1141 PROTECT, Université Paris Diderot- Sorbonne Paris Cité, Paris, France. [email protected].
⁹ Neuropediatrics and Metabolic Disorders Department, Reference Center for Leukodystrophies and Rare Leukoencéphalopathies (LEUKOFRANCE), CHU APHP Robert-Debré, Imen DORBOZ: INSERM U1141, Hopital Robert Debre, 48 boulevard Serurier, 75019, Paris, France. [email protected].

Abstract

Background: The etiology of intellectual disabilities is diverse and includes both genetic and environmental factors. The genetic causes of intellectual disabilities range from chromosomal aberrations to single gene disorders. The TRAPPC9 gene has been reported to cause autosomal recessive forms of intellectual disabilities in 56 patients from consanguineous and non-consanguineous families around the world.

Methods: We analyzed two siblings with intellectual disability, microcephaly and delayed motor and speech development from a consanguineous Sudanese family. Genomic DNA was screened for mutations using NGS panel (NextSeq500 Illumina) testing 173 microcephaly associated genes in the Molecular Genetics service in Robert Debre hospital in Paris, France.

Results: A novel homozygous mutation (NM_031466.7 (TRAPPC9):c.2288dup, p. (Val764Glyfs*7) in exon 14 of TRAPPC9 gene was found in the two patients. The mutation was predicted to cause nonsense mediated decay (NSMD) using SIFT prediction tool. The variant has not been found in either gnomAD or Exac databases. Both parents were heterozygous (carriers) to the mutation.

Conclusion: This is the first study to report patients with TRAPPC9-related disorder from Sub-Saharan Africa.

Keywords: Autosomal recessive; Intellectual disability; Novel; Sudan; TRAPPC9.

MeSH terms

Carrier Proteins / genetics
Humans
Intellectual Disability* / genetics
Intercellular Signaling Peptides and Proteins / genetics
Microcephaly* / genetics
Mutation
Pedigree

Substances

Carrier Proteins
Intercellular Signaling Peptides and Proteins