Recurrent partial rhombencephalosynapsis and holoprosencephaly in siblings with a mutation of ZIC2.
Recurrent partial rhombencephalosynapsis and holoprosencephaly in siblings with a mutation of ZIC2.
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DOI：
10.1002/ajmg.a.34029
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发表时间：
2011-07
影响因子：
2
通讯作者：
Clark, Gary D.
中科院分区：
文献类型：
--
作者：
Ramocki, Melissa B.;Scaglia, Fernando;Stankiewicz, Pawel;Belmont, John W.;Jones, Jeremy Y.;Clark, Gary D.
关键词：
菱形脑突触症是一种罕见的先天性脑畸形，其特征是小脑半球和齿状核融合，以及小脑发育不全或发育不全。虽然RES经常与其他脑畸形和/或先天性异常一起发现，但迄今为止尚未发现特定的分子病因学，也不存在动物模型。我们发现两个同父异母姐妹篇患有无叶或半叶前脑无裂畸形（HPE）和部分RES，这表明与HPE相关的基因也可能导致RES。ZIC 2基因外显子1中7个碱基对的缺失（c.392_98del7）在患有HPE和部分RES的两个同父异母姐妹篇中的每一个中鉴定出。为了鉴定RES的遗传原因并评估HPE中鉴定出的基因是否在RES之后，我们通过高分辨率染色体分析、染色体微阵列分析和四个HPE基因测序对另外11个RES患者进行了检测。没有发现ZIC 2或其他导致HPE的基因突变，这表明ZIC 2突变是与HPE相关的菱脑突触的罕见原因或贡献者。此外，一个人的染色体22q13.3和RES的复杂重排被确定，这表明存在一个剂量敏感的基因，可能有助于RES在这个区域。
Rhombencephalosynapsis (RES) is a rare congenital brain malformation typically identified by magnetic resonance imaging and characterized by fusion of the cerebellar hemispheres and dentate nuclei and vermian agenesis or hypogenesis. Although RES is frequently found in conjunction with other brain malformations and/or congenital anomalies, no specific molecular etiology has been discovered to date and no animal models exist. We identified two half sisters with alobar or semi-lobar holoprosencephaly (HPE) and partial RES, suggesting that genes linked to HPE may also contribute to RES. A deletion of seven base pairs in exon one of the ZIC2 gene (c.392_98del7) was identified in each of the two half sisters with HPE and partial RES. To identify genetic causes of RES and to assess whether genes identified in HPE have a role in RES, we tested 11 additional individuals with RES by high resolution chromosome analysis, chromosomal microarray analysis, and sequencing of four HPE genes. No mutations in ZIC2 or in other genes that cause HPE were identified, suggesting that mutation of ZIC2 is a rare cause of, or contributor to, rhombencephalosynapsis associated with HPE. In addition, an individual with a complex rearrangement of chromosome 22q13.3 and RES was identified, suggesting the presence of a dosage-sensitive gene that may contribute to RES in this region.
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染色体微阵列分析的临床实施：2513例产后病例的摘要。
影响因子：
3.7
作者：
Lu, Xinyan;Shaw, Chad A.;Patel, Ankita;Li, Jiangzhen;Cooper, M. Lance;Wells, William R.;Sullivan, Cathy M.;Sahoo, Trilochan;Yatsenko, Svetlana A.;Bacino, Carlos A.;Stankiewicz, Pawel;Ou, Zhishu;Chinault, A. Craig;Beaudet, Arthur L.;Lupski, James R.;Cheung, Sau W.;Ward, Patricia A.
通讯作者：
Ward, Patricia A.
影响因子：
4
作者：
Solomon BD;Lacbawan F;Mercier S;Clegg NJ;Delgado MR;Rosenbaum K;Dubourg C;David V;Olney AH;Wehner LE;Hehr U;Bale S;Paulussen A;Smeets HJ;Hardisty E;Tylki-Szymanska A;Pronicka E;Clemens M;McPherson E;Hennekam RC;Hahn J;Stashinko E;Levey E;Wieczorek D;Roeder E;Schell-Apacik CC;Booth CW;Thomas RL;Kenwrick S;Cummings DA;Bous SM;Keaton A;Balog JZ;Hadley D;Zhou N;Long R;Vélez JI;Pineda-Alvarez DE;Odent S;Roessler E;Muenke M
通讯作者：
Muenke M
影响因子：
5.3
作者：
Aruga, J;Inoue, T;Mikoshiba, K
通讯作者：
Mikoshiba, K
影响因子：
4.1
作者：
Schwahn, BC;Laryea, MD;Rozen, R
通讯作者：
Rozen, R
影响因子：
2.7
作者：
Elms, P;Siggers, P;Arkell, R
通讯作者：
Arkell, R