Novel and recurrent mutations in the TAT gene in Tunisian families affected with Richner–Hanhart Syndrome

Bouyacoub, Yosra; Zribi, H.; Azzouz, Hatem; Nasrallah, Fahmi; Abdelaziz, Rim Ben; Kacem, M.; Rekaya, Mariem Ben; Messaoud, Olfa; Romdhane, Lilia; Charfeddine, Chérine; Bouziri, Mustapha; Bouziri, Sonia; Tebib, Néji; Mokni, M.; Kaabachi, Naziha; Boubaker, Samir; Abdelhak, Sonia

doi:10.1016/j.gene.2013.07.066

Cited by 12 publications

(8 citation statements)

References 32 publications

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“…The tyrosine metabolism pathway plays an important role in biological processes and is related to the synthesis of neurotransmitters, hormones, and melanin. The dysfunction of the tyrosine metabolism pathway is related to a variety of diseases, including tyrosinemia, liver disease, and cancer [ 22 , 23 , 24 ] ( Figure 1 A). The final products of this metabolic pathway, fumarate and acetoacetate, are further converted into acetyl-CoA, which is involved in the biosynthesis of lipids.…”

Section: Resultsmentioning

confidence: 99%

Decreased SLC27A5 Suppresses Lipid Synthesis and Tyrosine Metabolism to Activate the Cell Cycle in Hepatocellular Carcinoma

et al. 2022

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Tyrosine is an essential ketogenic and glycogenic amino acid for the human body, which means that tyrosine is not only involved in protein metabolism, but also participates in the metabolism of lipids and carbohydrates. The liver is an important place for metabolism of lipids, carbohydrates, and proteins. The metabolic process of biological macro-molecules is a basis for maintaining the physiological activities of organisms, but the cross-linking mechanism of these processes is still unclear. Here, we found that the tyrosine-metabolizing enzymes, which were specifically and highly expressed in the liver, were significantly down-regulated in hepatocellular carcinoma (HCC), and had a correlation with a poor prognosis of HCC patients. Further analysis found that the reduction of tyrosine metabolism would activate the cell cycle and promote cell proliferation. In addition, we also found that the solute carrier family 27 member 5 (SLC27A5) regulates the expression of tyrosine-metabolizing enzymes through nuclear factor erythroid 2-related factor 2 (NRF2). Therefore, the SLC27A5 and tyrosine-metabolizing enzymes that we have identified coordinate lipid and tyrosine metabolism, regulate the cell cycle, and are potential targets for cancer treatment.

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Section: Resultsmentioning

confidence: 99%

Decreased SLC27A5 Suppresses Lipid Synthesis and Tyrosine Metabolism to Activate the Cell Cycle in Hepatocellular Carcinoma

et al. 2022

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“…Deficiency of TAT causes marked hypertyrosinemia, which leads to painful palmoplantar hyperkeratosis, pseudodendritic keratitis, and variable mental retardation (61). Recurrent mutation of the TAT gene has been reported in those affected by Richner-Hanhart syndrome (62). Fu et al (63) reported that downregulation of TAT at a frequently deleted region, 16q22, contributes to the pathogenesis of HCC, and it was demonstrated that TAT is a novel tumor suppressor gene.…”

Section: Discussionmentioning

confidence: 99%

Identification of prognostic biomarkers for patients with hepatocellular carcinoma after hepatectomy

et al. 2019

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Hepatocellular carcinoma (HCC) is a lethal malignancy with high morbidity and mortality rates worldwide. The identification of prognosis-associated biomarkers is crucial to improve HCC patient survival. The present study aimed to explore potential predictive biomarkers for HCC. Differentially expressed genes (DEGs) were analyzed in the GSE36376 dataset using GEO2R. Hub genes were identified and further investigated for prognostic value in HCC patients. A risk score model and nomogram were constructed to predict HCC prognosis using the prognosis-associated genes and clinical factors. Pearson's correlation was employed to show interactions among hub genes. Gene enrichment analysis was performed to identify detailed biological processes and pathways. A total of 71 DEGs were obtained and seven (ADH4, CYP2C8, CYP2C9, CYP8B1, SLC22A1, TAT and HSD17B13, all adjusted P≤0.05) of the 10 hub genes were identified as prognosis-related genes for survival analysis in HCC patients, including alcohol dehydrogenase 4 (class II), pi polypeptide (ADH4), cytochrome p450 family 2 subfamily C member 8 (CYP2C8), cytochrome P450 family 2 subfamily C member 9 (CYP2C9), cytochrome P450 family 8 subfamily B member 1 (CYP8B1), solute carrier family 22 member 1 (SLC22A1), tyrosine aminotransferase (TAT) and hydroxysteroid 17-β dehydrogenase 13 (HSD17B13). The risk score model could predict HCC prognosis and the nomogram visualized gene expression and clinical factors of probability for HCC prognosis. The majority of genes showed significant Pearson's correlations with others (41 Pearson correlations P≤0.01, four Pearson correlations P>0.05). GO analysis revealed that terms such as ‘chemical carcinogenesis’ and ‘drug metabolism-cytochrome P450’ were enriched and may prove helpful to elucidate the mechanisms of hepatocarcinogenesis. Hub genes ADH4, CYP2C8, CYP2C9, CYP8B1, SLC22A1, TAT and HSD17B13 may be useful as predictive biomarkers for HCC prognosis.

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“…Several mutations have been described for TAT , including complete deletion of both TAT alleles in one patient and a number of point mutations resulting in reduced enzymatic activity in other patients . In this study we detected two homozygous mutations in TAT : p.L312P (c.935T>C) and p.T408M (c.1223C>T).…”

Section: Discussionmentioning

confidence: 58%

Tyrosinemia type II: Novel mutations in TAT in a boy with unusual presentation

Gökay

Kendirci

Ustkoyuncu

et al. 2016

Pediatrics International

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Tyrosinemia type II is a rare autosomal recessive disorder caused by deficiency of tyrosine aminotransferase (TAT). It may occur with ocular and cutaneous symptoms with or without mental retardation, but epileptic seizure is a rare presentation of this disease. Herein we report the clinical, biochemical and genetic features of a 4-year-old boy who presented with afebrile seizure and photophobia. Genomic DNA was obtained from peripheral blood leukocytes from the whole family. Sequencing analysis was performed using the MiSeq next-generation sequencing platform. Sequencing of TAT indicated two new homozygous mutations p.L312P (c.935T>C) and p.T408M (c.1223C>T) for the proband and his asymptomatic sister. During a 2 year follow-up period, the patient had overall poor compliance with protein-restricted diet, but his asymptomatic sister had good compliance with the diet. Cognitive function of the patient worsened steadily, but his asymptomatic sister maintained normal mental status. Tyrosinemia type II should be considered in the differential diagnosis of children presenting with epileptic seizure and photophobia; furthermore, early diagnosis and protein-restricted regimen are important to reduce the risk of long-term complications of tyrosinemia type II such as mental disability.

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Novel and recurrent mutations in the TAT gene in Tunisian families affected with Richner–Hanhart Syndrome

Cited by 12 publications

References 32 publications

Decreased SLC27A5 Suppresses Lipid Synthesis and Tyrosine Metabolism to Activate the Cell Cycle in Hepatocellular Carcinoma

Decreased SLC27A5 Suppresses Lipid Synthesis and Tyrosine Metabolism to Activate the Cell Cycle in Hepatocellular Carcinoma

Identification of prognostic biomarkers for patients with hepatocellular carcinoma after hepatectomy

Tyrosinemia type II: Novel mutations in TAT in a boy with unusual presentation

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