Identification of novel LFNG mutations in spondylocostal dysostosis

Otomo, Nao; Mizumoto, Shuji; Lu, Hsing Fang; Takeda, Kazuki; Campos‐Xavier, Belinda; Mittaz-Crettol, Lauréane; Guo, Long; Takikawa, Kazuharu; Nakamura, Masaya; Yamada, Shuhei; Matsumoto, Morio; Watanabe, Kota; Ikegawa, Shiro

doi:10.1038/s10038-018-0548-2

Cited by 21 publications

(42 citation statements)

References 20 publications

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“…(E) Schematic representation of LFNG gene and localization of published mutations in patients with SCDO3. [1][2][3][4] The variant described in this study is located in exon 2 of LFNG (NM_001040167. LFNG belongs to the Fringe genes encoding a family of glycosyltransferases in the Notch signaling pathway and is localized to the Golgi.…”

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confidence: 93%

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Clinical and molecular delineation of spondylocostal dysostosis type 3

et al. 2021

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confidence: 93%

“…1 To date five patients with frameshift or missense variants in LFNG gene presenting with M-SDV were published. [1][2][3][4] Two individuals showed further minor nonspine-related anomalies (hernia, camptodactyly), but no major organ involvement has been described in SCDO3 patients so far.…”

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confidence: 99%

Clinical and molecular delineation of spondylocostal dysostosis type 3

et al. 2021

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“…Spondylocostal dysostosis (SCD) is a heterogeneous group of skeletal disorders characterized by congenital malformations of the vertebrae and ribs (Otomo et al, 2019). A homozygous mutation, p.Phe188Leu, in…”

Section: Spondylocostal Dysostosismentioning

confidence: 99%

“…for c.372delG (p.Lys124Asnfs*) and c.601G > A (p.Asp201Asn) variants of LFNG. The missense mutation exists in the DxD motif forming a catalytic site of the glycosyltransferase and causes loss of enzymatic activity of the mutant, suggesting that the disappearance of GlcNAcextension of O-fucose glycans likely causes SCD(Otomo et al, 2019).The recent screening of 78 patients with congenital scoliosis (CS) without a mutation in the known causative gene, TBX6, identified a patient with compound heterozygous missense variants in LFNG. The missense mutations, p.Leu156Arg and p.Arg286Trp, reported loss of the enzymatic activity(Takeda et al, 2018).…”

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confidence: 99%

Effects of Notch glycosylation on health and diseases

Urata

Takeuchi

2019

Dev Growth Differ

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Notch signaling is an evolutionarily conserved signaling pathway and is essential for cell-fate specification in metazoans. Dysregulation of Notch signaling results in various human diseases, including cardiovascular defects and cancer. In 2000, Fringe, a known regulator of Notch signaling, was discovered as a Notch-modifying glycosyltransferase. Since then, glycosylation-a post-translational modification involving literal sugars-on the Notch extracellular domain has been noted as a critical mechanism for the regulation of Notch signaling. Additionally, the presence of diverse Oglycans decorating Notch receptors has been revealed in the extracellular domain epidermal growth factor-like (EGF) repeats. Here, we concisely summarize the recent studies in the human diseases associated with aberrant Notch glycosylation. K E Y W O R D S

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“…Somite segmentation plays a crucial role in the proper formation of vertebrae and ribs in vertebrates. Spondylocostal dysostosis, a rare human genetic disorder, characterized by vertebral segmentation defects and malformations of ribs, is caused by autosomal recessive mutations of several genes related to somite segmentation such as DLL3 , HES7 , MESP2 , LFNG , TBX6 and RIPPLY2 (Turnpenny et al ; Whittock et al ; Sparrow et al ; Sparrow et al ; McInerney‐Leo et al ; Otomo et al ). In mice too, loss‐of‐function mutations of these orthologous genes recapitulate the phenotype observed in spondylocostal dysostosis (Kusumi et al ; Bessho et al ; Serth et al ; White et al ; Morimoto et al ; Makino et al ).…”

Section: Introductionmentioning

confidence: 99%

Role of somite patterning in the formation of Weberian apparatus and pleural rib in zebrafish

et al. 2019

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In the vertebrate body, a metameric structure is present along the anterior–posterior axis. Zebrafish tbx6−/− larvae, in which somite boundaries do not form during embryogenesis, were shown to exhibit abnormal skeletal morphology such as rib, neural arch and hemal arch. In this study, we investigated the role of somite patterning in the formation of anterior vertebrae and ribs in more detail. Using three‐dimensional computed tomography scans, we found that anterior vertebrae including the Weberian apparatus were severely affected in tbx6−/− larvae. In addition, pleural ribs of tbx6 mutants exhibited severe defects in the initial ossification, extension of ossification, and formation of parapophyses. Two‐colour staining revealed that bifurcation of ribs was caused by fusion or branching of ribs in tbx6−/−. The parapophyses in tbx6−/− juvenile fish showed irregular positioning to centra and abnormal attachment to ribs. Furthermore, we found that the ossification of the distal portion of ribs proceeded along myotome boundaries even in irregularly positioned myotome boundaries. These results provide evidence of the contribution of somite patterning to the formation of the Weberian apparatus and rib in zebrafish.

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Identification of novel LFNG mutations in spondylocostal dysostosis

Cited by 21 publications

References 20 publications

Clinical and molecular delineation of spondylocostal dysostosis type 3

Clinical and molecular delineation of spondylocostal dysostosis type 3

Effects of Notch glycosylation on health and diseases

Role of somite patterning in the formation of Weberian apparatus and pleural rib in zebrafish

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