OCRL1 mutation analysis in French Lowe syndrome patients: Implications for molecular diagnosis strategy and genetic counseling
OCRL1 mutation analysis in French Lowe syndrome patients: Implications for molecular diagnosis strategy and genetic counseling
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DOI：
10.1002/1098-1004(200008)16:2
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发表时间：
2000-01-01
期刊：
影响因子：
3.9
通讯作者：
Lunardi, J
中科院分区：
文献类型：
--
作者：
Monnier, N;Satre, V;Lunardi, J
Lowe 眼脑肾综合征 (OCRL) 是一种罕见的 X 连锁隐性遗传性疾病，其特征是严重的多效性表型，包括智力低下、双侧先天性白内障和肾范科尼综合征。负责 OCRL 的基因编码肌醇多磷酸-5-磷酸酶。我们对 36 个家族进行了突变分析，确定了 27 个新突变，其中两个是复发突变。这组突变由 27 个截短突变（移码、无义、剪接位点突变和大基因组缺失）、1 个框内缺失和 6 个错义突变组成。四个大的基因组缺失发生在基因的前半部分，而所有剩余的突变都发生在基因的第二部分，并且集中在几个外显子中。在寻找未知突变时，这种分布可能对筛查策略感兴趣。对家庭进行单倍型分析以分析突变位点的分离，并揭示了一个家庭中的体细胞嵌合现象。这是我们在受劳氏综合征影响的 44 个不相关家庭的总样本中描述的第二例嵌合现象。考虑到调查的家庭数量较少，看来体细胞和生发嵌合体在这种疾病中相当常见，必须在遗传咨询时考虑到。 Hum Mutat 16:157-165, 2000。(C) 2000 Wiley Liss, Inc.
The oculocerebrorenal syndrome of Lowe (OCRL) is a rare X-linked recessively inherited disease characterized by a severe pleiotropic phenotype including mental retardation, bilateral congenital cataract, and renal Fanconi syndrome. The gene responsible for OCRL encodes an inositol polyphosphate-5-phosphatase. We performed mutation analysis in 36 families and characterized 27 new mutations with two of them being recurrent mutations. The panel of mutations consisted of 27 truncating mutations (frameshift, nonsense, splice site mutations, and large genomic deletions), one in frame deletion, and six missense mutations. The four large genomic deletions occurred in the first half of the gene, whereas all the remaining mutations took place in the second part of the gene and were concentrated in a few exons. This distribution may be of interest in terms of screening strategy when looking for unknown mutations, Haplotyping of the families was performed to analyze segregation of the mutated loci, and revealed a somatic mosaicism in one family This is the second case of mosaicism we characterized in a total panel of 44 unrelated families affected by Lowe's syndrome. Considering the low number of families investigated, it appeared that somatic and germinal mosaicisms are quite common in this disease and must be taken into account for genetic counseling. Hum Mutat 16:157-165, 2000. (C) 2000 Wiley Liss, Inc.