TRAPPC9-CDG: A novel congenital disorder of glycosylation with dysmorphic features and intellectual disability

Radenkovic, Silvia; Martinelli, Diego; Zhang, Yuebo; Preston, Graeme; Maiorana, Arianna; Terracciano, Alessandra; Dentici, Maria Lisa; Pisaneschi, Elisa; Novelli, Antonio; Ranatunga, Wasantha; Ligęzka, Anna; Ghesquière, Bart; Deyle, David R.; Kozicz, Tamás; Vairo, Filippo Pinto e; Witters, Peter; Morava, Éva

doi:10.1016/j.gim.2021.12.012

Cited by 19 publications

(30 citation statements)

References 40 publications

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“…TRAPPC9 -related intellectual disability is an autosomal recessive disease with particular overrepresentation in consanguineous communities [ 4 – 12 ]. To our knowledge, only 56 patients were reported to have mutations in TRAPPC9 gene [ 4 – 12 , 14 , 15 , 17 – 25 ]. The majority of these patients were from Middle Eastern consanguineous families (Table 1 .).…”

Section: Discussionmentioning

confidence: 99%

“…The clinical features of the two siblings in our study are aligned with those reported with TRAPPC9 mutations. More recently, missense mutations in TRAPPC9 gene have been reported in three patients with intellectual disability and biochemical abnormalities consistent with Congenital disorder of glycosylation [ 17 ]. This underlies the clinical heterogeneity of TRAPPC9- related disorder.…”

Section: Discussionmentioning

confidence: 99%

“…So far, mutations in TRAPPC9 gene have been reported in very few families around the world [ 4 – 12 , 14 , 15 , 17 – 25 ] but none from Sub-Saharan Africa. In this study, we reported a novel homozygous mutation in TRAPPC9 gene causing autosomal recessive intellectual disability in a consanguineous family from Sudan.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2022

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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

et al. 2022

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“…TRAPPC9 is a subunit of the highly conserved protein complex called the transport protein particle ( TRAPP ), a guanine nucleotide exchange factor for rab proteins that operates in secretory, endocytic, and autophagic pathways ( 26 ). Over half of the patients with TRAPPC9 mutations are reported to present different degrees of obesity ( 27 ). Hnoonual et al ( 12 ) found that the deletion of the TRAPPC9 gene leads to obesity.…”

Section: Discussionmentioning

confidence: 99%

Identification of TRAPPC9 and BAIAP2 Gene Polymorphisms and Their Association With Fat Deposition-Related Traits in Hu Sheep

et al. 2022

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Fat deposition is an important economic trait that is closely related to feed efficiency and carcass performance in livestock. In this study, the fat deposition-related traits of 1,293 Hu sheep were measured and descriptive statistical analysis was conducted. The results showed that the coefficient of variation of all fat deposition-related traits was higher than 24%. In addition, single nucleotide polymorphisms and the expression characteristics of TRAPPC9 (encoding trafficking protein particle complex subunit 9) and BAIAP2 (encoding brain-specific Angiogenesis inhibitor 1-associated protein 2) genes in Hu sheep were detected using PCR amplification, Sanger sequencing, KASPar genotyping, and quantitative real-time reverse transcription PCR (qRT-PCR). The associations between SNPs and fat deposition-related traits were also analyzed. Two intronic mutations, TRAPPC9 g.57654 A > G and BAIAP2 g.46061 C > T, were identified in Hu sheep. The result of association analysis showed that TRAPPC9 g.57654 A > G and BAIAP2 g.46061 C > T were both significantly associated with the weight of tail fat, tail fat relative weight (body weight), and tail fat relative weight (carcass) (P < 0.05). Comprehensive effects analysis showed that there were significant differences between the combined genotypes and tail fat and perirenal fat deposition. Moreover, qRT-PCR analysis showed that TRAPPC9 and BAIAP2 are widely expressed, and their expression levels were significantly higher in the small-tail group compared with those in the big-tail group (P < 0.01). These results provided important candidate molecular markers that could be used in strategies to reduce tail fat deposition in Hu sheep.

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“…However, it is more plausible that PGM2L1 has a regulatory role in sugar metabolism in the brain and, in that way, causes the neurodevelopmental disorder seen in the patients. Another enzyme defect that was examined for glycosylation defects was related to a deficiency in the trafficking protein particle complex subunit 9 (TRAPPC9) [ 67 ]. For metabolites directly linked to glycosylation, higher UDP-hexose levels and lower levels of sialic acid were found in the patient cells, which is indicative of a CDG.…”

Section: In Vitro Metabolomicsmentioning

confidence: 99%

Understanding Inborn Errors of Metabolism through Metabolomics

Driesen

Witters

2022

Metabolites

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Inborn errors of metabolism (IEMs) are rare diseases caused by a defect in a single enzyme, co-factor, or transport protein. For most IEMs, no effective treatment is available and the exact disease mechanism is unknown. The application of metabolomics and, more specifically, tracer metabolomics in IEM research can help to elucidate these disease mechanisms and hence direct novel therapeutic interventions. In this review, we will describe the different approaches to metabolomics in IEM research. We will discuss the strengths and weaknesses of the different sample types that can be used (biofluids, tissues or cells from model organisms; modified cell lines; and patient fibroblasts) and when each of them is appropriate to use.

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TRAPPC9-CDG: A novel congenital disorder of glycosylation with dysmorphic features and intellectual disability

Cited by 19 publications

References 40 publications

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

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

Identification of TRAPPC9 and BAIAP2 Gene Polymorphisms and Their Association With Fat Deposition-Related Traits in Hu Sheep

Understanding Inborn Errors of Metabolism through Metabolomics

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