Familial-skewed X-chromosome inactivation as a predisposing factor for late-onset X-linked sideroblastic anemia in carrier females.
Familial-skewed X-chromosome inactivation as a predisposing factor for late-onset X-linked sideroblastic anemia in carrier females.
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DOI：
10.1182/blood.v96.13.4363
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发表时间：
2000-12
期刊：
影响因子：
20.3
通讯作者：
M. Cazzola;A. May;G. Bergamaschi;P. Cerani;V. Rosti;D. Bishop
中科院分区：
文献类型：
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作者：
M. Cazzola;A. May;G. Bergamaschi;P. Cerani;V. Rosti;D. Bishop
X连锁铁粒幼细胞性贫血（XLSA）是由红系特异性5-氨基乙酰丙酸合酶（ALAS 2）基因突变引起的。老年妇女谁提出了获得性铁粒幼细胞性贫血的研究。分子分析显示她是ALAS 2基因错义突变的杂合子，但她只在网织红细胞中表达突变基因。她的两个女儿和一个孙女是这种突变的杂合子，血红蛋白水平正常，网织红细胞中表达正常的ALAS 2基因。一名先前诊断为中间型地中海贫血的孙子被发现是ALAS 2突变的半合子。吡哆醇治疗完全纠正了先证者和她孙子的贫血。在这个家庭中分析的所有妇女都表现出白细胞中的X染色体失活，这表明与不平衡的里昂化相关的遗传性疾病。由于优先活跃的X染色体携带突变的ALAS 2等位基因，老年人获得性偏斜可能使遗传条件恶化，并消除了先证者的正常ALAS 2等位基因表达。（血。2000;96：4363-4365）
X-linked sideroblastic anemia (XLSA) is caused by mutations in the erythroid-specific 5-aminolevulinic acid synthase (ALAS2) gene. An elderly woman who presented with an acquired sideroblastic anemia is studied. Molecular analysis revealed that she was heterozygous for a missense mutation in the ALAS2 gene, but she expressed only the mutated gene in reticulocytes. Her 2 daughters and a granddaughter were heterozygous for this mutation, had normal hemoglobin levels, and expressed the normal ALAS2 gene in reticulocytes. A grandson with a previous diagnosis of thalassemia intermedia was found to be hemizygous for the ALAS2 mutation. Treatment with pyridoxine completely corrected the anemia both in the proband and her grandson. All women who were analyzed in this family showed skewed X-chromosome inactivation in leukocytes, which indicated a hereditary condition associated with unbalanced lyonization. Because the preferentially active X chromosome carried the mutant ALAS2 allele, acquired skewing in the elderly likely worsened the genetic condition and abolished the normal ALAS2 allele expression in the proband. (Blood. 2000;96:4363-4365)