Autosomal recessive hypotrichosis with loose anagen hairs associated with
            <i>TKFC</i>
            mutations*

Onoufriadis, Alexandros; Cabezas, Alicia; Ng, Joseph C.F.; Canales, José; Costas, Marı́a Jesús; Ribeiro, João Meireles; Rodrigues, Joaquim Rui; McAleer, Maeve A.; Castelo‐Soccio, Leslie; Simpson, Michael A.; Fraternali, Franca; Irvine, Alan D.; Cameselle, José Carlos; McGrath, John A.

doi:10.1111/bjd.19481

Cited by 7 publications

(9 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This is a matter of global interest, since the vast majority of human genomes encode for Thr185-TKFC. Anyone intending to approach these questions from the point of view of human metabolism of fructose would need to be aware that Thr185-TKFC, if it actually fails to favour lipogenesis and hepatic accumulation of triglycerides in humans as it does in mice [10], is not biochemically 'null' as triokinase ( [1,19] and Fig. 2).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

The TKFC Ala185Thr variant, reported as ‘null’ for fructose metabolism, is fully active as triokinase

et al. 2022

Self Cite

View full text Add to dashboard Cite

TKFC‐encoded triokinase catalyses glyceraldehyde phosphorylation in fructose metabolism and favours lipogenesis in mice. In Tkfc knockouts or knockdowns, fructose oxidation predominates over lipogenesis. The highly prevalent human variant Ala185Thr‐Triokinase/FMN cyclase (TKFC) has been reported to be ‘null’ for fructose metabolism, since Ala185‐TKFC rescues the mouse TKFC‐deficient phenotype, whereas Ala185Thr‐TKFC does not. Such report implies that most humans would display a noncanonical fructose metabolism, but it ignores the well‐characterized triokinase activity of Ala185Thr‐TKFC. Here, earlier evidence is summarized, along with new evidence that both human variants are equally active in yeast. Therefore, future research on triokinase in the context of human fructose metabolism should consider that Ala185Thr‐TKFC is not biochemically ‘null’.

show abstract

Section: Discussionmentioning

confidence: 99%

“…2). This assay does not detect GA kinase activity, but it should be noticed that all the point mutations applied to Thr185-TKFC affect similarly DHA kinase and GA kinase [1,18,19].…”

Section: Human Thr185-tkfc Is Fully Active As Triokinasementioning

confidence: 99%

The TKFC Ala185Thr variant, reported as ‘null’ for fructose metabolism, is fully active as triokinase

et al. 2022

Self Cite

View full text Add to dashboard Cite

show abstract

“…Onoufriadis et al 4 . propose a genetically determined enzyme abnormality to account for loose anagen occurring with hypotrichosis.…”

Section: Figurementioning

confidence: 99%

“…Whole‐exome sequencing (WES) has been used to identify genes responsible for a range of dermatological disorders, 5 but sequence analysis data must be carefully interpreted and various assumptions are required to make sense of the large number of variants detected. Onoufriadis et al 4 . applied WES to 15 families with children showing features of loose anagen.…”

Section: Figurementioning

confidence: 99%

“…2 It has therefore been suggested that variation in KRT75 (OMIM *609025), encoding a keratin of the inner root sheath companion layer, may account for loose anagen and unruly hair. 3 Onoufriadis et al 4 propose a genetically determined enzyme abnormality to account for loose anagen occurring with hypotrichosis. Recessive mutations in TKFC, the gene encoding an enzyme named triokinase and flavin mononucleotide cyclase, were detected in one compound heterozygous case, from a total of 15 families studied.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Translational genetics: a challenging but important path

Brown

2020

Br J Dermatol

View full text Add to dashboard Cite

A review of genotrichoses and hair pathology associated with inherited skin diseases

Doolan

Rayinda

Chiu

et al. 2023

British Journal of Dermatology

View full text Add to dashboard Cite

Genetic hair disorders, also known as genotrichoses, are characterized by abnormalities of hair structure, growth, or differentiation, giving rise to a spectrum of phenotypes such as hypertrichosis, hypotrichosis and atrichia. These disorders may present as isolated phenotypes or be part of more complex phenotypes including abnormalities in skin or other organs. Genetic discoveries for hair disorders have been recently augmented with the advent of next-generation sequencing (NGS) technologies. We reviewed the literature and summarised disease-gene associations for inherited hair disorders, as well as genodermatoses presenting with hair abnormalities discovered by NGS technologies. We identified 28 non-syndromic hair disorders, involving 25 individual genes and four unidentified genes. We have also discovered that approximately 30% of all genodermatoses that were identified by NGS approaches demonstrated hair abnormalities as part of their phenotype. This review underscores the huge impact of NGS technologies in disclosing the genetics of hair disorders and the potential the discoveries provide for future translational research and new therapies.

show abstract

Autosomal recessive hypotrichosis with loose anagen hairs associated with TKFC mutations*

Abstract: The authors declare they have no conflicts of interest.• Loose anagen hairs are loosely anchored and can be easily plucked from the scalp.• To date, no gene pathology has been associated with loose anagen syndrome.

Cited by 7 publications

References 42 publications

The TKFC Ala185Thr variant, reported as ‘null’ for fructose metabolism, is fully active as triokinase

The TKFC Ala185Thr variant, reported as ‘null’ for fructose metabolism, is fully active as triokinase

Translational genetics: a challenging but important path

A review of genotrichoses and hair pathology associated with inherited skin diseases

Contact Info

Product

Resources

About