Mutation of the LUNATIC FRINGE Gene in Humans Causes Spondylocostal Dysostosis with a Severe Vertebral Phenotype

Sparrow, Duncan B.; Chapman, Gavin; Wouters, Merridee A.; Whittock, Neil V.; Ellard, Sian; Fatkin, Diane; Turnpenny, Peter D.; Kusumi, Kenro; Sillence, David; Dunwoodie, Sally L.

doi:10.1086/498879

Cited by 224 publications

(218 citation statements)

References 55 publications

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“…On sequencing the entire coding region and splice sites of the LFNG gene, a homozygous missense mutation (c.564CϾA) in exon 3 was detected (Sparrow et al, 2006), resulting in substitution of leucine for phenylalanine (F188L). The proband's parents, with normal spinal anatomy, were both heterozygous for the mutant allele.…”

Section: Lunatic Fringementioning

confidence: 99%

Abnormal vertebral segmentation and the notch signaling pathway in man

Turnpenny

Alman

Cornier

et al. 2007

Developmental Dynamics

145

120

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Abnormal vertebral segmentation (AVS) in man is a relatively common congenital malformation but cannot be subjected to the scientific analysis that is applied in animal models. Nevertheless, some spectacular advances in the cell biology and molecular genetics of somitogenesis in animal models have proved to be directly relevant to human disease. Some advances in our understanding have come through DNA linkage analysis in families demonstrating a clustering of AVS cases, as well as adopting a candidate gene approach. Only rarely do AVS phenotypes follow clear Mendelian inheritance, but three genes-DLL3, MESP2, and LNFG-have now been identified for spondylocostal dysostosis (SCD). SCD is characterized by extensive hemivertebrae, trunkal shortening, and abnormally aligned ribs with points of fusion. In familial cases clearly following a Mendelian pattern, autosomal recessive inheritance is more common than autosomal dominant and the genes identified are functional within the Notch signaling pathway. Other genes within the pathway cause diverse phenotypes such as Alagille syndrome (AGS) and CADASIL, conditions that may have their origin in defective vasculogenesis. Here, we deal mainly with SCD and AGS, and present a new classification system for AVS phenotypes, for which, hitherto, the terminology has been inconsistent and confusing.

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Section: Lunatic Fringementioning

confidence: 99%

Abnormal vertebral segmentation and the notch signaling pathway in man

Turnpenny

Alman

Cornier

et al. 2007

Developmental Dynamics

145

120

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“…Mutations of Fringe give Notch signaling defects that manifest at developmental boundaries in the formation of wings, legs and eyes in Drosophila [7]. In mammals, including humans [48], Lfng is required for Notch signaling during somitogenesis, and affects female meiosis [49] and T cell development in mice [47]. In vivo functions of Rfng are not noticeably developmental [10] and Mfng mutant mice have not been described.…”

Section: Abbreviationsmentioning

confidence: 99%

Regulation of Notch signaling by glycosylation

Stanley

2007

Current Opinion in Structural Biology

122

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“…Accordingly, mutations in the lunatic fringe gene (LFNG, OMIM ID: 602576) (Fig. 4) encoding a 1-3 GlcNAc-transferase elongating O-Fuc have been described in cases of spondylocostal dysostosis [68].…”

Section: Lunatic Fringementioning

confidence: 99%

Diseases of glycosylation beyond classical congenital disorders of glycosylation

Hennet

2012

Biochimica et Biophysica Acta (BBA) - General Subjects

117

103

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BACKGROUND: Diseases of glycosylation are rare inherited disorders, which are often referred to as congenital disorders of glycosylation (CDG). Several types of CDG have been described in the last decades, encompassing defects of nucleotide-sugar biosynthesis, nucleotide-sugar transporters, glycosyltransferases and vesicular transport. Although clinically heterogeneous, most types of CDG are associated with neurological impairments ranging from severe psychomotor retardation to moderate intellectual disabilities. CDG are mainly caused by defects of N-glycosylation, owing to the simple detection of under-glycosylated serum transferrin by isoelectric focusing. SCOPE OF REVIEW: In the last years, several disorders of O-glycosylation, glycolipid and glycosaminoglycan biosynthesis have been described, which are known by trivial names not directly associated with the family of CDG. The present review outlines 64 gene defects affecting glycan biosynthesis and modifications, thereby underlining the complexity of glycosylation pathways and pointing to unexpected phenotypes and functional redundancies in the control of glycoconjugate biosynthesis. MAJOR CONCLUSIONS: The increasing application of whole-genome sequencing techniques unravels new defects of glycosylation, which are associated to moderate forms of mental disabilities. GENERAL SIGNIFICANCE: The knowledge gathered through the investigation of CDG increases the understanding of the functions associated to protein glycosylation in humans. This article is part of a Special Issue entitled Glycoproteomics.

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Mutation of the LUNATIC FRINGE Gene in Humans Causes Spondylocostal Dysostosis with a Severe Vertebral Phenotype

Cited by 224 publications

References 55 publications

Abnormal vertebral segmentation and the notch signaling pathway in man

Abnormal vertebral segmentation and the notch signaling pathway in man

Regulation of Notch signaling by glycosylation

Diseases of glycosylation beyond classical congenital disorders of glycosylation

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