An Indian child with Kindler syndrome resulting from a new homozygous nonsense mutation (C468X) in the KIND1 gene
An Indian child with Kindler syndrome resulting from a new homozygous nonsense mutation (C468X) in the KIND1 gene
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DOI：
10.1111/j.1365-2230.2004.01712.x
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发表时间：
2005-05-01
影响因子：
4.1
通讯作者：
McGrath, JA
中科院分区：
文献类型：
--
作者：
Sethuraman, G;Fassihi, H;McGrath, JA
Kindler综合征是一种遗传性皮肤病，表现为水泡，随后是光敏性和进行性色素沉着。这种疾病是由编码蛋白质kindlin-1的KIND 1基因突变引起的，kindlin-1是一种最近表征的677个氨基酸的蛋白质，参与肌动蛋白细胞骨架与细胞外基质的锚定。我们报告的临床特征，一个11岁的男孩与金德勒综合征从一个血缘关系的印度家庭和鉴定的纯合无义突变（C468 X）在外显子12的KIND 1基因在他的基因组DNA。这种突变以前没有描述过，但与以前发表的17种KIND 1突变相似，这些突变都被预测会导致Kindlin-1蛋白表达和功能的丧失。这个男孩的临床特征突出了kindlin-1在皮肤生物学中的相关性，特别是表皮粘附和对急性和慢性日光暴露的反应。KIND 1中这种新的致病性突变的描述对于该家族的遗传咨询和评估未受影响的家族成员的携带者状态也是有用的。
Kindler syndrome is an inherited skin condition that presents with blistering followed by photosensitivity and a progressive poikiloderma. The disorder results from mutations in the KIND1 gene, encoding the protein kindlin-1, a recently characterized 677-amino acid protein involved in anchorage of the actin cytoskeleton to the extracellular matrix. We report the clinical features of an 11-year-old boy with Kindler syndrome from a consanguineous Indian family and the identification of a homozygous nonsense mutation (C468X) in exon 12 of the KIND1 gene in his genomic DNA. This mutation has not been described previously but is similar to the 17 previously published KIND1 mutations that are all predicted to lead to loss of kindlin-1 protein expression and function. The clinical features in this boy highlight the relevance of kindlin-1 in skin biology, specifically to epidermal adhesion and response to acute and chronic sun exposure. Delineation of this new pathogenic mutation in KIND1 is also useful for genetic counselling in this family and in assessing carrier status in unaffected family members.