Analysis of FOXF1 and the FOX gene cluster in patients with VACTERL association.
Analysis of FOXF1 and the FOX gene cluster in patients with VACTERL association.
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DOI：
10.1016/j.ejmg.2011.01.007
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发表时间：
2011-05
影响因子：
1.9
通讯作者：
Solomon BD
中科院分区：
文献类型：
--
作者：
Agochukwu NB;Pineda-Alvarez DE;Keaton AA;Warren-Mora N;Raam MS;Kamat A;Chandrasekharappa SC;Solomon BD
脊椎相关性是一种相对常见的疾病，发生率约为20，000 - 35，000例出生中的1例，是出生缺陷的非随机相关性，包括脊椎缺陷（V）、肛门闭锁（A）、心脏缺陷（C）、气管食管瘘（TE）、肾脏异常（R）和肢体畸形（L）。虽然病因是未知的，在大多数患者，有证据表明，它是因果异质性。几项研究表明，在Vapril的遗传证据，这意味着遗传位点的作用。最近，发现具有VEGF-L组分特征和致死性发育性肺部疾病（肺泡毛细血管发育不良伴肺静脉错位（ACD/MPV））的患者存在影响FOXF 1和染色体16 q24上FOX基因簇的缺失或突变。我们通过直接测序和高密度SNP微阵列研究了12例VEGF-L相关但无ACD/MPV的患者的该基因。我们的FOXF 1突变分析显示正常序列，没有影响研究患者染色体16 q24上FOX基因簇的基因组不平衡。这些结果的可能解释包括VEGIL相关性的病因学和临床异质性，影响该基因的突变可能仅发生在受影响更严重的个体中，以及研究样本量不足。
VACTERL association, a relatively common condition with an incidence of approximately 1 in 20,000 – 35,000 births, is a non-random association of birth defects that includes vertebral defects (V), anal atresia (A), cardiac defects (C), tracheo-esophageal fistula (TE), renal anomalies (R) and limb malformations (L). Although the etiology is unknown in the majority of patients, there is evidence that it is causally heterogeneous. Several studies have shown evidence for inheritance in VACTERL, implying a role for genetic loci. Recently, patients with component features of VACTERL and a lethal developmental pulmonary disorder, alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV), were found to harbor deletions or mutations affecting FOXF1 and the FOX gene cluster on chromosome 16q24. We investigated this gene through direct sequencing and high-density SNP microarray in 12 patients with VACTERL association but without ACD/MPV. Our mutational analysis of FOXF1 showed normal sequences and no genomic imbalances affecting the FOX gene cluster on chromosome 16q24 in the studied patients. Possible explanations for these results include the etiologic and clinical heterogeneity of VACTERL association, the possibility that mutations affecting this gene may occur only in more severely affected individuals, and insufficient study sample size.