A combination of two novels homozygous FCSK variants cause disorder of glycosylation with defective fucosylation: New patient and literature review

Manoochehri, Jamal; Kamal, Neda; Khamirani, Hossein Jafari; Zoghi, Sina; Haghighi, Maryam Fazelzadeh; Goodarzi, Hamed; Tabei, Seyed Mohammad Bagher

doi:10.1016/j.ejmg.2022.104535

Cited by 5 publications

(6 citation statements)

References 28 publications

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“…have confirmed the significant decrease of fucokinase, FCSK ‐encoded protein, in patients and the created CRISPR/Cas9 FCSK knockout HAP1 cell line, they have not seen any detectable fucosylation change in the fibroblast and serum samples of patients, and FCSK knockout cells (Ng, Rosenfeld, et al., 2018 ). Their two reported cases and the subsequent reported ones, FCSK‐CDG patients, manifested intellectual disability, developmental delay, seizure, epilepsy, gait problems, hypotonia, contractures, abnormal brain MRI, feeding difficulty, and ophthalmological disorders (Al Tuwaijri et al., 2023 ; Manoochehri et al., 2022 ; Ng, Rosenfeld, et al., 2018 ; Ozgun & Sahin, 2022 ).…”

Section: Discussionmentioning

confidence: 99%

“…in two unrelated patients with severe multisystem manifestations such as brain anomalies, intellectual disability, developmental delay, intractable seizures accompanied by epileptic encephalopathy, muscle contractures, hypotonia, walking disability, poor feeding, difficulty in gastric emptying, and ocular disorders (Ng, Rosenfeld, et al., 2018 ). Subsequently, three other patients with different pathogenic variants in the FCSK gene have been reported, including one by our team (Al Tuwaijri et al., 2023 ; Manoochehri et al., 2022 ; Ozgun & Sahin, 2022 ). Table 1 displays the characteristics of all FCSK‐CDG patients documented thus far (Al Tuwaijri et al., 2023 ; Manoochehri et al., 2022 ; Ng, Rosenfeld, et al., 2018 ; Ozgun & Sahin, 2022 ).…”

Section: Introductionmentioning

confidence: 91%

“…T A B L E 1 Molecular and clinical characterization of CDGF2 patients (Al Tuwaijri et al, 2023;Manoochehri et al, 2022;Ng, Rosenfeld, et al, 2018;Ozgun & Sahin, 2022). U-87 MG cells were seeded in a 6-well cell culture plate, and 80% confluency was achieved after 24 h; they were co-transfected by guide-1 and guide-2 CRISPR/Cas9 constructs utilizing Lipofectamine 3000 (Thermo Fisher Scientific) according to the manufacturer's instruction.…”

Section: Cell Culturementioning

confidence: 99%

“…Subsequently, three other patients with different pathogenic variants in the FCSK gene have been reported, including one by our team (Al Tuwaijri et al, 2023;Manoochehri et al, 2022;Ozgun & Sahin, 2022). Table 1 displays the characteristics of all FCSK-CDG patients documented thus far (Al Tuwaijri et al, 2023;Manoochehri et al, 2022;Ng, Rosenfeld, et al, 2018;Ozgun & Sahin, 2022).…”

Section: Introductionmentioning

confidence: 97%

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Novel insight into FCSK‐congenital disorder of glycosylation through a CRISPR‐generated cell model

Fazelzadeh Haghighi,

Jafari Khamirani,

Fallahi

et al. 2024

Molec Gen & Gen Med

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BackgroundFCSK‐congenital disorder of glycosylation (FCSK‐CDG) is a recently discovered rare autosomal recessive genetic disorder with defective fucosylation due to mutations in the fucokinase encoding gene, FCSK. Despite the essential role of fucokinase in the fucose salvage pathway and severe multisystem manifestations of FCSK‐CDG patients, it is not elucidated which cells or which types of fucosylation are affected by its deficiency.MethodsIn this study, CRISPR/Cas9 was employed to construct an FCSK‐CDG cell model and explore the molecular mechanisms of the disease by lectin flow cytometry and real‐time PCR analyses.ResultsComparison of cellular fucosylation by lectin flow cytometry in the created CRISPR/Cas9 FCSK knockout and the same unedited cell lines showed no significant change in the amount of cell surface fucosylated glycans, which is consistent with the only documented previous study on different cell types. It suggests a probable effect of this disease on secretory glycoproteins. Investigating O‐fucosylation by analysis of the NOTCH3 gene expression as a potential target revealed a significant decrease in the FCSK knockout cells compared with the same unedited ones, proving the effect of fucokinase deficiency on EGF‐like repeats O‐fucosylation.ConclusionThis study expands insight into the FCSK‐CDG molecular mechanism; to the best of our knowledge, it is the first research conducted to reveal a gene whose expression level alters due to this disease.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 91%

Section: Cell Culturementioning

confidence: 99%

Section: Introductionmentioning

confidence: 97%

See 2 more Smart Citations

Novel insight into FCSK‐congenital disorder of glycosylation through a CRISPR‐generated cell model

Fazelzadeh Haghighi,

Jafari Khamirani,

Fallahi

et al. 2024

Molec Gen & Gen Med

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“…Genetic analysis of the extracted genomic DNA from the peripheral blood samples was performed by whole exome sequencing (WES), as in the previous studies 4,5 . The presence of the detected variant was confirmed by Sanger sequencing.…”

Section: Methodsmentioning

confidence: 99%

Novel insight into the ectodermal dysplasia 11A: Splicing variant of the EDARADD gene in a family with clinical variability and literature review

Haghighi

Kamal

Khamirani

et al. 2023

The Journal of Dermatology

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Pathogenic variants in the EDARADD gene result in autosomal recessive and autosomal dominant ectodermal dysplasia. This article reports on the fourth family in the world with ectodermal dysplasia 11A (ECTD11A) cause from a novel splicing variant in the EDARADD gene, identified by whole exome sequencing and confirmed by Sanger sequencing. The proband and his mother were heterozygous for the detected variant (NM_145861.4:c.161‐2A>T). The proband manifests unusual symptoms including hyperkeratotic plaques, slow‐growing hair, recurrent infection, and pectus excavatum. His mother presents hypohidrosis, extensive tooth decay, fragile nails, and sparse hair. Further studies on ECTD11A patients could be useful to characterizing the phenotype features more precisely.

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The third patient of ACACA-related acetyl-CoA carboxylase deficiency with seizure and literature review

Shafieipour

Khamirani

Kamal

et al. 2023

European Journal of Medical Genetics

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A combination of two novels homozygous FCSK variants cause disorder of glycosylation with defective fucosylation: New patient and literature review

Cited by 5 publications

References 28 publications

Novel insight into FCSK‐congenital disorder of glycosylation through a CRISPR‐generated cell model

Novel insight into FCSK‐congenital disorder of glycosylation through a CRISPR‐generated cell model

Novel insight into the ectodermal dysplasia 11A: Splicing variant of the EDARADD gene in a family with clinical variability and literature review

The third patient of ACACA-related acetyl-CoA carboxylase deficiency with seizure and literature review

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