Chromosome 11p15 Paternal Isodisomy in Focal Forms of Neonatal Hyperinsulinism
Chromosome 11p15 Paternal Isodisomy in Focal Forms of Neonatal Hyperinsulinism
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DOI：
10.1210/jc.2008-0673
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发表时间：
2008-12-01
影响因子：
5.8
通讯作者：
Jaubert, F.
中科院分区：
文献类型：
--
作者：
Damaj, L.;le Lorch, M.;Jaubert, F.
内容：局灶性先天性高胰岛素血症是由于位于11p15.1区域的ABCC 8基因中的父系起源的组成性杂合突变，其频率高于KCNJ 11基因。这种突变与病变中母系遗传的11p15.1至11p15.5区域的丢失有关。材料与方法：应用免疫组织化学和荧光原位杂交技术，对β细胞间期核进行了研究，并将两个基因的探针定位于该区域（ABCC 8和CDKN 1C基因）在四例局灶性高胰岛素血症病例中进行。4例局灶性先天性高胰岛素血症患者病变中的β细胞为11号和13号染色体二倍体。11p15.1 ~ 11p15.2和11p15.4 ~ 11p15.5区域分别含有ABCC 8和CDKN 1C基因，存在两个拷贝。在这些病灶与微卫星标记侧翼的ABCC 8和CDKN 1C基因，而在ABCC 8基因的杂合突变的损失被证实从father.Conclusions：有一个重复的父亲的等位基因在11号染色体上的高胰岛素血症病灶的焦点形式。所观察到的父系同二体性使得β细胞对于ABCC 8突变是纯合的，并且在病变中具有与在弥漫性形式的先天性高胰岛素血症中观察到的类似的K通道缺陷。（临床内分泌代谢杂志93：4941-4947，2008）
Context: Focal forms of congenital hyperinsulinism are due to a constitutional heterozygous mutation of paternal origin in the ABCC8 gene, more often than the KCNJ11 gene, located in the 11p15.1 region. This mutation is associated with the loss of the maternally inherited 11p15.1 to 11p15.5 region in the lesion. We investigated the possible occurrence of a compensatory duplication of the paternal 11p15.1-11p15.5 region.Materials and Methods: A combined immunohistochemistry and fluorescent in situ hybridization study on beta-cell interphase nuclei with probes covering two genes located in this region (ABCC8 and CDKN1C genes) was performed in four cases of focal forms of hyperinsulinism.Results: beta-Cells in the lesions of four cases of focal congenital hyperinsulinism were diploid for chromosomes 11 and 13. The 11p15.1 to 11p15.2 and 11p15.4 to 11p15.5 regions containing ABCC8 and CDKN1C genes, respectively, were present with two copies. Loss of the maternal allele was confirmed in these focal lesions with microsatellite markers flanking the ABCC8 and CDKN1C genes, whereas a heterozygous mutation in the ABCC8 gene was inherited from the father.Conclusions: There is a duplication of the paternal allele on chromosome 11 in the focal forms of hyperinsulinism lesion. The paternal isodisomy observed rendered the beta-cells homozygous for ABCC8 mutation and harbored a K-channel defect in the lesion similar to that observed in diffuse forms of congenital hyperinsulinism. (J Clin Endocrinol Metab 93: 4941-4947, 2008)