Corrigendum to “Improvement of regressive autism symptoms in a child with <i>TMLHE</i> deficiency following carnitine supplementation”

Ziats, Mark N.; Comeaux, Matthew S.; Yang, Yaping; Scaglia, Fernando; Elsea, Sarah H.; Sun, Qin; Beaudet, Arthur L.; Schaaf, Christian P.

doi:10.1002/ajmg.a.37192

Cited by 9 publications

(15 citation statements)

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“…Evidence from the literature suggests that TMLHE and VAMP7 could play a role in domestication through modulation of behaviour. TMLHE is the first enzyme in the carnitine biosynthesis pathway, and TMLHE deficiency causes regressive autism symptoms that can be improved via carnitine supplementation (Ziats et al., ). It is worth noting also that a region containing a gene involved in autism in human was detected when comparing two lines of quail divergently selected on social behaviour (Fariello et al., ).…”

Section: Discussionmentioning

confidence: 99%

A guinea fowl genome assembly provides new evidence on evolution following domestication and selection in galliformes

Vignal

Boitard

Thébault

et al. 2019

Molecular Ecology Resources

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The helmeted guinea fowl Numida meleagris belongs to the order Galliformes. Its natural range includes a large part of sub‐Saharan Africa, from Senegal to Eritrea and from Chad to South Africa. Archaeozoological and artistic evidence suggest domestication of this species may have occurred about 2,000 years BP in Mali and Sudan primarily as a food resource, although villagers also benefit from its capacity to give loud alarm calls in case of danger, of its ability to consume parasites such as ticks and to hunt snakes, thus suggesting its domestication may have resulted from a commensal association process. Today, it is still farmed in Africa, mainly as a traditional village poultry, and is also bred more intensively in other countries, mainly France and Italy. The lack of available molecular genetic markers has limited the genetic studies conducted to date on guinea fowl. We present here a first‐generation whole‐genome sequence draft assembly used as a reference for a study by a Pool‐seq approach of wild and domestic populations from Europe and Africa. We show that the domestic populations share a higher genetic similarity between each other than they do to wild populations living in the same geographical area. Several genomic regions showing selection signatures putatively related to domestication or importation to Europe were detected, containing candidate genes, most notably EDNRB 2 , possibly explaining losses in plumage coloration phenotypes in domesticated populations.

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Section: Discussionmentioning

confidence: 99%

A guinea fowl genome assembly provides new evidence on evolution following domestication and selection in galliformes

Vignal

Boitard

Thébault

et al. 2019

Molecular Ecology Resources

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“…Deletions in the TMLHE gene on Xq28 (GRCh38: X:155,489,010–155,612,960) encoding for ε-N-trimethyllysine hydroxylase (Enzyme 3 in Fig. 7) have been associated with non-syndromic autism-spectrum disorders in males [163–166]. The TMLHE exon 2 deletion is relatively common even in healthy males with an estimated frequency of 1:350 males, but is more frequent in patients with autism, suggesting that ε-N-trimethyllysine hydroxylase deficiency is a risk factor for autism (meta-analysis Z-score = 2.90 and p = 0.00037), although with low penetrance (2 to 4%) [164].…”

Section: Carnitine Biosynthesismentioning

confidence: 99%

Carnitine transport and fatty acid oxidation

Longo

Frigeni

Pasquali

2016

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

631

506

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Carnitine is essential for the transfer of long-chain fatty acids across the inner mitochondrial membrane for subsequent β-oxidation. It can be synthesized by the body or assumed with the diet from meat and dairy products. Defects in carnitine biosynthesis do not routinely result in low plasma carnitine levels. Carnitine is accumulated by the cells and retained by kidneys using OCTN2, a high affinity organic cation transporter specific for carnitine. Defects in the OCTN2 carnitine transporter results in autosomal recessive primary carnitine deficiency characterized by decreased intracellular carnitine accumulation, increased losses of carnitine in the urine, and low serum carnitine levels. Patients can present early in life with hypoketotic hypoglycemia and hepatic encephalopathy, or later in life with skeletal and cardiac myopathy or sudden death from cardiac arrhythmia, usually triggered by fasting or catabolic state. This disease responds to oral carnitine that, in pharmacological doses, enters cells using the amino acid transporter B0,+. Primary carnitine deficiency can be suspected from the clinical presentation or identified by low levels of free carnitine (C0) in the newborn screening. Some adult patients have been diagnosed following the birth of an unaffected child with very low carnitine levels in the newborn screening. The diagnosis is confirmed by measuring low carnitine uptake in the patients’ fibroblasts or by DNA sequencing of the SLC22A5 gene encoding the OCTN2 carnitine transporter. Some mutations are specific for certain ethnic backgrounds, but the majority are private and identified only in individual families. Although the genotype usually does not correlate with metabolic or cardiac involvement in primary carnitine deficiency, patients presenting as adults tend to have at least one missense mutation retaining residual activity.

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“…At the metabolic level, we identified the relationship between folate deficiency and the TMLHE gene deficiency. TMLHE deficiency syndrome has been repeatedly associated with ASD [Celestino‐Soper et al, ; Nava et al, ; Ning et al ; Ziats et al, ]. We assume that folate deficiency in ASD could lead to a similar or milder metabolic disruption compared to that described in TMLHE deficiency and thereby contribute to its development and progression.…”

Section: Discussionmentioning

confidence: 99%

Identification of likely associations between cerebral folate deficiency and complex genetic‐ and metabolic pathogenesis of autism spectrum disorders by utilization of a pilot interaction modeling approach

et al. 2017

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Recently, cerebral folate deficiency (CFD) was suggested to be involved in the pathogenesis of autism spectrum disorders (ASD). However, the exact role of folate metabolism in the pathogenesis of ASD, identification of underlying pathogenic mechanisms and impaired metabolic pathways remain unexplained. The aim of our study was to develop and test a novel, unbiased, bioinformatics approach in order to identify links between ASD and disturbed cerebral metabolism by focusing on abnormal folate metabolism, which could foster patient stratification and novel therapeutic interventions. An unbiased, automatable, computational workflow interaction model was developed using available data from public databases. The interaction network model of ASD-associated genes with known cerebral expression and function (SFARI) and metabolic networks (MetScape), including connections to known metabolic substrates, metabolites and cofactors involving folates, was established. Intersection of bioinformatically created networks resulted in a limited amount of interaction modules pointing to common disturbed metabolic pathways, linking ASD to CFD. Two independent interaction modules (comprising three pathways) covering enzymes encoded by ASD-related genes and folate cofactors utilizing enzymes were generated. Module 1 suggested possible interference of CFD with serine and lysine metabolism, while module 2 identified correlations with purine metabolism and inosine monophosphate production. Since our approach was primarily conceived as a proof of principle, further amendments of the presented initial model are necessary to obtain additional actionable outcomes. Our modelling strategy identified not only previously known interactions supported by evidence-based analyses, but also novel plausible interactions, which could be validated in subsequent functional and/or clinical studies. Autism Res 2017, 10: 1424-1435. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.

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Corrigendum to “Improvement of regressive autism symptoms in a child with TMLHE deficiency following carnitine supplementation”

Cited by 9 publications

References 0 publications

A guinea fowl genome assembly provides new evidence on evolution following domestication and selection in galliformes

A guinea fowl genome assembly provides new evidence on evolution following domestication and selection in galliformes

Carnitine transport and fatty acid oxidation

Identification of likely associations between cerebral folate deficiency and complex genetic‐ and metabolic pathogenesis of autism spectrum disorders by utilization of a pilot interaction modeling approach

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