Characterization of a germline mosaicism in families with Lowe syndrome, and identification of seven novel mutations in the OCRL1 gene.
Characterization of a germline mosaicism in families with Lowe syndrome, and identification of seven novel mutations in the OCRL1 gene.
复制标题
Lowe 综合征家族生殖系嵌合体的表征，以及 OCRL1 基因中七个新突变的鉴定。
DOI：
10.1086/302443
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发表时间：
1999
影响因子：
9.8
通讯作者：
Joël Lunardi
中科院分区：
文献类型：
--
作者：
V. Satre;Nicole Monnier;Florence Berthoin;C. Ayuso;Alain Joannard;P. Jouk;Isidora López;André Megabarne;Henri Jean Philippe;Henri Plauchu;María Luisa de Torres;Joël Lunardi
眼脑肾综合征（OCRL）是一种X连锁疾病，其特征是眼睛、神经系统和肾脏的主要异常。OCRL1基因的突变与该疾病有关。OCRL 1编码磷脂酰肌醇4，5-二磷酸（PtdIns [4，5] P2）5-磷酸酶。我们检测了8名不相关的OCRL患者的OCRL1基因，发现了7个新的突变和1个复发性框内缺失。在新的突变中，两个无义突变（R317X和E558X）和其他三个移码突变导致蛋白质的提前终止。错义突变R483G位于高度保守的PtdIns（4，5）P2 5-磷酸酶结构域。最后，一个移码突变，2799delC，修改了OCRL 1的C-末端部分，延长了6个氨基酸。总的来说，70%的错义突变位于外显子15，52%的突变聚集在外显子11 - 15。我们还确定了两个新的微卫星标记的OCRL 1位点，我们检测到一个家庭的生殖嵌合体。这一观察结果对Lowe综合征家庭的遗传咨询有直接影响。
The oculocerebrorenal syndrome of Lowe (OCRL) is an X-linked disorder characterized by major abnormalities of eyes, nervous system, and kidneys. Mutations in the OCRL1 gene have been associated with the disease. OCRL1 encodes a phosphatidylinositol 4, 5-biphosphate (PtdIns[4,5]P2) 5-phosphatase. We have examined the OCRL1 gene in eight unrelated patients with OCRL and have found seven new mutations and one recurrent in-frame deletion. Among the new mutations, two nonsense mutations (R317X and E558X) and three other frameshift mutations caused premature termination of the protein. A missense mutation, R483G, was located in the highly conserved PtdIns(4,5)P2 5-phosphatase domain. Finally, one frameshift mutation, 2799delC, modifies the C-terminal part of OCRL1, with an extension of six amino acids. Altogether, 70% of missense mutations are located in exon 15, and 52% of all mutations cluster in exons 11-15. We also identified two new microsatellite markers for the OCRL1 locus, and we detected a germline mosaicism in one family. This observation has direct implications for genetic counseling of Lowe syndrome families.