Late‐onset ornithine transcarbamylase deficiency in male patients: Prognostic factors and characteristics of plasma amino acid profile

Harada, Eimei; Nishiyori, Atsushi; Tokunaga, Yasuyuki; Watanabe, Yoriko; Kuriya, Norikazu; Kumashiro, Ryukichi; Kuno, Toshiki; Kuromaru, Ryuichi; Hirose, Shinichi; Ichikawa, Kotaro; Yoshino, Makoto

doi:10.1111/j.1442-200x.2006.02181.x

Cited by 27 publications

(32 citation statements)

References 34 publications

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“…In our previous series of Japanese families, the c.119G4A (p.R40H) mutation was encountered in a cluster. 7,10,15 In addition, we identified another novel mutation, c.163T4G (p.Y55D) in two discrete families. 10,16 It is not known whether or not these mutations share a common ancestral origin or have arisen recurrently.…”

Section: Introductionmentioning

confidence: 91%

“…4 However, there are some male patients in whom the onset of the disease is delayed until the preschool age period 5 through to adulthood. 6,7 Some affected males within the same families may remain asymptomatic for life. 8 Their condition is now recognized as 'late-onset OTC deficiency in male patients' , accounting for B30% of male patients.…”

Section: Introductionmentioning

confidence: 99%

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Mutant alleles associated with late-onset ornithine transcarbamylase deficiency in male patients have recurrently arisen and have been retained in some populations

et al. 2009

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We performed haplotype analysis using nine single nucleotide polymorphisms in the ornithine transcarbamylase gene to explore the ancestral origins of three mutations associated with late-onset phenotype in male patients: p.R40H, p.R277W and p.Y55D. Overall, 8 haplotypes were defined among 14 families carrying p.R40H, 5 families carrying p.R277W and 2 families with p.Y55D mutations. Of nine Japanese families carrying p.R40H, eight exhibited haplotype (HT)1, whereas the other family harbored HT2. Among three Caucasian families, one Spanish and one Australian family bore HT3; one Austrian family had HT4. Two US patients harbored HT2 and HT4. Among families carrying p.R277W, HT5 was found in one Japanese, one Korean and one US family. Two other US families had HT2 and HT6. Two families carrying p.Y55D, both Japanese, shared HT1. These results indicate that the p.R40H mutation has arisen recurrently in all populations studied, although there is evidence for a founder effect in Japan, with most cases probably sharing a common origin, and to a lesser extent in subjects of European ancestry (HT3). It is evident that p.R277W mutation has recurred in discrete populations. The p.Y55D mutation appears to have arisen from a common ancestor, because this transversion (c.163T4G) occurs rarely.

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Section: Introductionmentioning

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Mutant alleles associated with late-onset ornithine transcarbamylase deficiency in male patients have recurrently arisen and have been retained in some populations

et al. 2009

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“…Patients 1 through 10 are reported elsewhere (Yoshino et al 1990;Nishiyori et al 1997;Harada et al 2006). In this earlier series, one patient was available from each family, and accordingly, the patient number corresponds to that of the family number.…”

Section: Patientsmentioning

confidence: 99%

“…However, the R40H mutation has been found in discrete families in the Japanese population (Matsuda et al 1996;Nishiyori et al 1997;Harada et al 2006) and in other ethnic groups (Tuchman et al 1995;Plöchl et al 1999;Arranz et al 2007). The R277W mutation was also found in multiple families with different ethnic origins (Finkelstein et al 1990b;Hata et al 1991;Matsuura et al 1993; present series).…”

Section: Introductionmentioning

confidence: 99%

Paternal transmission and slow elimination of mutant alleles associated with late-onset ornithine transcarbamylase deficiency in male patients

et al. 2007

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In ten families with late-onset ornithine transcarbamylase (OTC) deficiency in male patients, three mutant alleles-R40H, R277W, and Y55D-were identified. In a total of 20 informative parent-offspring pairs, father-to-daughter transmission and mother-to-offspring transmission occurred in five (25%) and 15 (75%), respectively, indicating that paternal transmission contributes substantially to the pool of these mutant alleles. Relative reproductive fitness of males and females carrying the mutant alleles was calculated to be 0.49 and 0.89, respectively. Comparison of the life span of the mutant alleles, estimated on the basis of these fitness values with those associated with classic phenotype (neonatal onset) in which reproductive fitness of male patients was nil, revealed that mutant alleles associated with the late-onset phenotype were eliminated more slowly. This would allow the late-onset phenotype mutant alleles to be retained more frequently in a population than those associated with classic phenotype. Although heterozygous females carrying the late-onset phenotype mutant alleles were generally asymptomatic, one female carrying the R40H allele died after a hyperammonemic episode at the age of 18 years. Such heterozygous females should be alerted to possible hyperammonemic crisis.

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“…Hemizygous males with complete OTC deficiency display severe hyperammonemia within the first week(s) of life. Although males and heterozygous females with subtotal defects frequently present later, adult-onset OTC deficiency is rare [3][4][5] and found mostly in females with unfavorable lyonization.…”

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confidence: 99%

Ornithine transcarbamylase (OTC) deficiency based on a hemizygous p.R277W mutation causing life-threatening hyperammonemic crisis during treatment for Hodgkin’s lymphoma

et al. 2010

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Late‐onset ornithine transcarbamylase deficiency in male patients: Prognostic factors and characteristics of plasma amino acid profile

Cited by 27 publications

References 34 publications

Mutant alleles associated with late-onset ornithine transcarbamylase deficiency in male patients have recurrently arisen and have been retained in some populations

Mutant alleles associated with late-onset ornithine transcarbamylase deficiency in male patients have recurrently arisen and have been retained in some populations

Paternal transmission and slow elimination of mutant alleles associated with late-onset ornithine transcarbamylase deficiency in male patients

Ornithine transcarbamylase (OTC) deficiency based on a hemizygous p.R277W mutation causing life-threatening hyperammonemic crisis during treatment for Hodgkin’s lymphoma

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