Ancestral founder mutation of the nude (FOXN1) gene in congenital severe combined immunodeficiency associated with alopecia in southern Italy population
Ancestral founder mutation of the nude (FOXN1) gene in congenital severe combined immunodeficiency associated with alopecia in southern Italy population
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DOI：
10.1046/j.1529-8817.2004.00091.x
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发表时间：
2004-05-01
影响因子：
1.9
通讯作者：
Pignata, C
中科院分区：
文献类型：
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作者：
Adriani, M;Martinez-Mir, A;Pignata, C
FOXN1 转录因子在胸腺上皮和皮肤中选择性表达，其基因改变导致小鼠和人类的 Nude/SCID 表型。第一个描述的人类 FOXN1 突变是外显子 5 中的 C792T 转变，导致无义突变 R255X，并在来自意大利南部一个小社区的两名先证者中检测到。在这个社区，另外四名患有先天性脱发的儿童因严重感染而在幼儿期死亡。在这项研究中，我们报告了对 30% 村庄人口的这种突变的筛查。这项分析使我们从 843 名筛查居民中鉴定出 55 名 R255X 突变杂合携带者 (6.52%)。一项家谱研究表明，这些受试者属于 39 个家族，在一个由 483 个人组成的 7 代谱系中存在关联。通过档案数据库，一对出生于 19 世纪初的祖上夫妇被确定。为了确认突变的祖先起源，我们对位于 17 号染色体上 FOXN1 基因侧翼的两个微卫星标记 D17S2187 和 D17S1880 进行了基因分型。鉴定出的三个单倍型 3/R255X/3、3/R255X/2 和 3/R255X/1 与该突变的单一祖先起源一致。 R255X。
Genetic alterations of the FOXN1 transcription factor, selectively expressed in thymic epithelia and skin, are responsible in both mice and humans for the Nude/SCID phenotype. The first described human FOXN1 mutation was a C792T transition in exon 5 resulting in the nonsense mutation R255X, and was detected in two probands originated from a small community in southern Italy. In this community, four additional children affected with congenital alopecia died in early childhood because of severe infections. In this study, we report on the screening for this mutation in 30% of the village population. This analysis led us to identify 55 heterozygous carriers (6.52%) of the R255X mutation out of 843 inhabitants screened. A genealogical study revealed that these subjects, belonging to 39 families, were linked in an extended 7-generational pedigree comprising 483 individuals. Through the archival database a single ancestral couple, born at the beginning of the 19th century, was identified. To confirm the ancestral origin of the mutation we genotyped two microsatellite markers, D17S2187 and D17S1880, flanking the FOXN1 gene on chromosome 17. The three haplotypes identified, 3/R255X/3, 3/R255X/2 and 3/R255X/1, are consistent with a single ancestral origin for the mutation R255X.