Novel mutations in the CLN6 gene causing a variant late infantile neuronal ceroid lipofuscinosis.
Novel mutations in the CLN6 gene causing a variant late infantile neuronal ceroid lipofuscinosis.
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CLN6 基因的新突变导致变异型晚期婴儿神经元蜡样质脂褐质沉着症。
DOI：
10.1002/humu.10207
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发表时间：
2003
期刊：
影响因子：
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通讯作者：
Boustany,Rose-Mary
中科院分区：
文献类型：
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作者：
Teixeira,CarlaA;Espinola,Janice;Huo,Liang;Kohlschutter,Johannes;PersaudSawin,Dixie-Ann;Minassian,Berge;Bessa,CarlosJP;Guimaraes,A;Stephan,DietrichA;SaMiranda,MariaClara;MacDonald,MarcyE;Ribeiro,MariaGil;Boustany,Rose-Mary
神经元蜡样质脂褐质沉积症（NCL）是一组异质性的常染色体隐性遗传神经退行性疾病，包括Batten和其他相关疾病以及许多变体。其特征在于进行性神经元细胞死亡。CLN 6基因是最近发现的，突变导致了一种变异的晚期婴儿型NCL（vLINCL）。我们描述了四个新的突变theCLN 6基因。这使得38个家族中已知的CLN 6突变总数达到11个。这表明CLN 6基因可能是高度可变的。1例爱尔兰/法国/美洲原住民血统的美国患者在外显子3中的4 bp插入（c.267_268insAACG）为杂合子。另一个等位基因在外显子7上有一个点突变（c.898T>C），导致W300 R氨基酸改变。两名印度裔特立尼达兄弟姐妹在外显子4的5′供体剪接位点（IVS 4 +1G>T）突变为纯合子，影响内含子4开始处不变GT的第一个碱基。第四个新的突变，4 bp和1 bp的外显子7（c.829_832delGTCG;c.837delG）的双缺失，被确定在葡萄牙患者杂合子的I154 del PortugueseCLN 6突变。11个突变中有4个位于外显子4。三名葡萄牙患者的临床资料类似于CLN 6患者没有缺陷的CLN 6或其他已知的NCL基因的描述。我们得出以下结论：1）CLN 6基因可能是一个高度可变的基因; 2）外显子4必须编码一段对功能至关重要的蛋白质; 3）葡萄牙的vLINCL疾病具有遗传异质性; 4）I154 del占受影响的CLN 6葡萄牙等位基因的81.25%; 5）3例vLINCL葡萄牙患者可能存在新的NCL基因缺陷。2003年，《突变》21：502-508。© 2003 Wiley利斯公司
The neuronal ceroid lipofuscinoses (NCLs) are a heterogeneous group of autosomal recessive neurodegenerative diseases comprising Batten and other related diseases plus numerous variants. They are characterized by progressive neuronal cell death. TheCLN6gene was recently identified, mutations in which cause one of the variant late infantile forms of NCL (vLINCL). We describe four novel mutations in theCLN6gene. This brings the total number ofCLN6mutations known to 11 in 38 families. This suggests that theCLN6gene may be highly mutable. An American patient of Irish/French/Native American origin was heterozygous for a 4‐bp insertion (c.267_268insAACG) in exon 3. The other allele had a point mutation (c.898T>C) in exon 7 resulting in a W300R amino acid change. Two Trinidadian siblings of Indian origin were homozygous for a mutation at the 5′ donor splice site of exon 4 (IVS4+1G>T), affecting the first base of the invariant GT at the beginning of intron 4. The fourth novel mutation, a double deletion of 4 bp and 1 bp in exon 7 (c.829_832delGTCG;c.837delG), was identified in a Portuguese patient heterozygous for the I154del PortugueseCLN6mutation. Four of the 11 mutations identified are in exon 4. Three Portuguese patients with clinical profiles similar toCLN6patients without defects inCLN6or other known NCL genes are described. We conclude the following: 1) theCLN6gene may be a highly mutable gene; 2) exon 4 must code for a segment of the protein crucial for function; 3) vLINCL disease in Portugal is genetically heterogeneous; 4) the I154del accounts for 81.25% of affectedCLN6Portuguese alleles; and 5) three vLINCL Portuguese patients may have defects in a new NCL gene. Hum Mutat 21:502–508, 2003. © 2003 Wiley‐Liss, Inc.