Mutations in the urocanase gene UROC1 are associated with urocanic aciduria

Espinós, Carmen; Pineda, Merçè; Martínez‐Rubio, Dolores; Lupo, Vincenzo; Ormazábal, Aída; Vilaseca, M. A.; Spaapen, L. J. M.; Palau, Francesc; Artuch, Rafael

doi:10.1136/jmg.2008.060632

Cited by 19 publications

(10 citation statements)

References 22 publications

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“…We investigated in silico the biological relevance of the MPZ p.S121F mutation as previously described ( Espinos et al, 2009 ) . The residue S121 is an evolutionary conserved amino acid, invariant across more than 100 different species (data not shown).…”

Section: Methods and Resultsmentioning

confidence: 99%

Congenital hypomyelinating neuropathy due to a novel MPZ mutation

Sevilla

Lupo

Sivera

et al. 2011

Journal of the Peripheral Nervous System

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Congenital hypomyelinating neuropathy (CHN) is a severe inherited neuropathy with neonatal or early infancy onset, reduced nerve conduction velocity, and pathological evidence of hypomyelination. We describe a case of CHN that presented with neonatal hypotonia and a progressive downhill clinical course, developing cranial nerve dysfunction, and respiratory failure. The nerve conduction velocities were severely slowed and sural nerve biopsy revealed non-myelinated and poorly myelinated axons, with no typical onion bulbs. The mutational screening showed that our proband harbored a novel missense mutation, p.S121F, in the MPZ gene. In silico analyses and molecular modeling predicted that the replacement of a serine by a phenylalanine is a non-tolerated change and may affect the folding and the stability of the protein. Subcellular location studies were performed and revealed that the mutant protein loses its correct location on the cell membrane surface and is mainly expressed in the cytosol, reducing its adhesive properties. This case illustrates the clinical heterogeneity that exists in neuropathies associated with MPZ mutations and highlights that in patients with mild hypotonia in the first months that develop a very severe demyelinating neuropathy, the MPZ gene must be taken into account.

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Section: Methods and Resultsmentioning

confidence: 99%

Congenital hypomyelinating neuropathy due to a novel MPZ mutation

Sevilla

Lupo

Sivera

et al. 2011

Journal of the Peripheral Nervous System

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“…Intermittent ataxia can also be seen in Hartnup disease; additional symptoms are pellagra-like skin changes, photic dermatitis, and psychiatric symptoms (Kleta et al 2004). Recently a new cause of intermittent ataxia and mental retardation due to urocanic aciduria in a patient with mutations in the urocanase gene has been described (Espinó s et al 2009).…”

Section: Intermittent/episodic Ataxiasmentioning

confidence: 99%

Inborn errors of metabolism and motor disturbances in children

García‐Cazorla

Wolf

Serrano

et al. 2009

J of Inher Metab Disea

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Summary Motor disturbances are very common in paediatric neurology. Often families can be reassured that these are just variants of normal development. However, abnormal movements can also be the hallmark of severe brain dysfunction of different and complex origins. This review concentrates on motor disturbances as frequent and important symptoms of inborn errors of metabolism. A structured diagnostic approach is developed taking into account age-dependent physiological developments and pathophysiological responses of gross and fine motor functions. A series of investigations are presented with the primary aim of early diagnosis of treatable conditions. The correct recognition and differentiation of movement disorders (ataxia, rigid akinetic syndrome (Fparkinsonism_), dystonia, athetosis, tremor, and others), spasticity, and neuromuscular disorders, requires profound neurological expertise. A high level of suspicion and close interaction between paediatric neurologists and specialists in inborn errors of metabolism are indispensable to effectively and timely identify patients in whom motor disturbances are the presenting and/or main symptom of an inborn error. Abbreviations

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“…Like histidase, it is widely distributed within the bacterial domain, though less so in the archaeal and eukaryotic domains. The amino acid sequence is highly conserved (29,76). For example, the urocanase of Pseudomonas shares about 35% identity with the human UROC1 gene product over the 500-amino-acid stretch corresponding to the bacterial enzyme (Table 1).…”

Section: Urocanasementioning

confidence: 99%

Regulation of the Histidine Utilization (Hut) System in Bacteria

Bender

2012

Microbiol Mol Biol Rev

122

128

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SUMMARY The ability to degrade the amino acid histidine to ammonia, glutamate, and a one-carbon compound (formate or formamide) is a property that is widely distributed among bacteria. The four or five enzymatic steps of the pathway are highly conserved, and the chemistry of the reactions displays several unusual features, including the rearrangement of a portion of the histidase polypeptide chain to yield an unusual imidazole structure at the active site and the use of a tightly bound NAD molecule as an electrophile rather than a redox-active element in urocanase. Given the importance of this amino acid, it is not surprising that the degradation of histidine is tightly regulated. The study of that regulation led to three central paradigms in bacterial regulation: catabolite repression by glucose and other carbon sources, nitrogen regulation and two-component regulators in general, and autoregulation of bacterial regulators. This review focuses on three groups of organisms for which studies are most complete: the enteric bacteria, for which the regulation is best understood; the pseudomonads, for which the chemistry is best characterized; and Bacillus subtilis , for which the regulatory mechanisms are very different from those of the Gram-negative bacteria. The Hut pathway is fundamentally a catabolic pathway that allows cells to use histidine as a source of carbon, energy, and nitrogen, but other roles for the pathway are also considered briefly here.

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Mutations in the urocanase gene UROC1 are associated with urocanic aciduria

Cited by 19 publications

References 22 publications

Congenital hypomyelinating neuropathy due to a novel MPZ mutation

Congenital hypomyelinating neuropathy due to a novel MPZ mutation

Inborn errors of metabolism and motor disturbances in children

Regulation of the Histidine Utilization (Hut) System in Bacteria

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