Paternal transmission and slow elimination of mutant alleles associated with late-onset ornithine transcarbamylase deficiency in male patients
Paternal transmission and slow elimination of mutant alleles associated with late-onset ornithine transcarbamylase deficiency in male patients
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DOI：
10.1007/s10038-007-0212-8
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发表时间：
2008-01-01
影响因子：
3.5
通讯作者：
Yoshino, Makoto
中科院分区：
文献类型：
--
作者：
Numata, Sanae;Harada, Eimei;Yoshino, Makoto
在10个迟发性鸟氨酸转氨甲酰酶（OTC）缺乏症男性家系中，发现了3个突变等位基因R40H、R277W和Y55D。在总共20个信息丰富的亲子对中，分别有5个（25%）和15个（75%）发生了父女传播和母子传播，这表明父源传播对这些突变等位基因的库有很大贡献。携带突变等位基因的雄性和雌性的相对生殖适合度分别为0.49和0.89。突变等位基因的寿命的比较，估计这些健身值的基础上与经典的表型（新生儿发病），其中男性患者的生殖健身为零，揭示了与晚发型表型相关的突变等位基因被淘汰得更慢。这将允许晚发型表型突变等位基因在群体中比与经典表型相关的等位基因更频繁地保留。虽然携带晚发型表型突变等位基因的杂合子女性通常无症状，但一名携带R40 H等位基因的女性在18岁时死于高氨血症发作。这种杂合子女性应警惕可能的高氨血症危象。
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.