Kindelan S A, Brook A H, Gangemi L, Lench N, Wong F S, Fearne J, Jackson Z, Foster G, Stringer B M
Department of Child Dental Health, School of Clinical Dentistry, University of Sheffield, Claremont Crescent, UK.
J Dent Res. 2000 Dec;79(12):1978-82. doi: 10.1177/00220345000790120901.
Amelogenesis imperfecta (AI) is a heterogeneous group of inherited disorders of defective enamel formation. The major protein involved in enamel formation, amelogenin, is encoded by a gene located at Xp22.1-Xp22.3. This study investigated the molecular defect producing a combined phenotype of hypoplasia and hypomineralization in a family with the clinical features and inheritance pattern of X-linked amelogenesis imperfecta (XAI). Genomic DNA was prepared from buccal cells sampled from family members. The DNA was subjected to the polymerase chain-reaction (PCR) in the presence of a series of oligonucleotide primers designed to amplify all 7 exons of the amelogenin gene. Cloning and sequencing of the purified amplification products identified a cytosine deletion in exon VI at codon 119. The deletion resulted in a frameshift mutation, introducing a premature stop signal at codon 126, producing a truncated protein lacking the terminal 18 amino acids. Identifying mutations assists our understanding of the important functional domains within the gene, and finding another novel mutation emphasizes the need for family-specific diagnosis of amelogenesis imperfecta.
釉质发育不全（AI）是一组异质性的遗传性疾病，其特征为釉质形成缺陷。参与釉质形成的主要蛋白质——釉原蛋白，由位于Xp22.1-Xp22.3的一个基因编码。本研究调查了一个具有X连锁釉质发育不全（XAI）临床特征和遗传模式的家族中，导致发育不全和矿化不足联合表型的分子缺陷。从家庭成员的颊细胞中提取基因组DNA。在一系列旨在扩增釉原蛋白基因所有7个外显子的寡核苷酸引物存在的情况下，对DNA进行聚合酶链反应（PCR）。对纯化的扩增产物进行克隆和测序，确定外显子VI第119密码子处有一个胞嘧啶缺失。该缺失导致移码突变，在第126密码子处引入一个提前终止信号，产生一种缺少末端18个氨基酸的截短蛋白。识别突变有助于我们了解该基因内重要的功能域，发现另一个新突变强调了对釉质发育不全进行家族特异性诊断的必要性。
