Novel mutations in ALOX12B in patients with autosomal recessive congenital ichthyosis and evidence for genetic heterogeneity on chromosome 17p13
Novel mutations in ALOX12B in patients with autosomal recessive congenital ichthyosis and evidence for genetic heterogeneity on chromosome 17p13
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DOI：
10.1038/sj.jid.5700640
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发表时间：
2007-04-01
影响因子：
6.5
通讯作者：
Fischer, Judith
中科院分区：
文献类型：
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作者：
Lesueur, Fabienne;Bouadjar, Bakar;Fischer, Judith
我们报告了来自11个常染色体隐性遗传先天性鱼鳞病（ARCI）家族的20例患者的临床和分子研究结果，这些患者与染色体17p13连锁，并归因于ALOX基因簇的突变，该基因簇包括三个脂氧合酶基因ALOX 3、ALOX 12 B和ALOX 15 B。我们在11个家系中仅发现了6个新的错义突变和1个新的缺失，导致ALOX 12 B提前终止密码子，这使我们研究了ALOX 15 B的可能意义。该基因的突变分析，以及ALOXE3，这是已知的突变在某些情况下的ARCI，未能揭示致病突变在其余五个ARCI家族，表明染色体17p13上的其他基因可能参与这种疾病。然而，通过在非大疱性先天性鱼鳞病样红皮病的ALOX 12 B突变库中添加新的变体，我们的数据有助于扩大突变谱，以开发有效的分子遗传学检测，用于分析携带者状态未知的高危个体。
We report clinical and molecular findings in 20 patients from 11 families with autosomal recessive congenital ichthyosis (ARCI) linked to chromosome 17p13, and attributed to mutations in the ALOX gene cluster, which includes three lipoxygenase genes, ALOXE3, ALOX12B, and ALOX15B. We identified six novel missense mutations and one novel deletion leading to a premature stop codon in ALOX12B in only six out of the 11 familes which led us to investigate a possible implication of ALOX15B. Mutation analysis of this gene, as well as ALOXE3, which is known to be mutated in some cases of ARCI, failed to reveal causative mutations in the five remaining ARCI families, indicating that other genes on chromosome 17p13 may be involved in this disease. However, by adding new variants to the repertoire of ALOX12B mutations in non-bullous congenital ichthyosiform erythroderma, our data contribute to an enlargement of the spectrum of mutations for the development of efficient molecular genetic tests for analysis of at risk individuals whose carrier status is unknown.