Four novel RSK2 mutations in females with Coffin-Lowry syndrome

被引:15
作者
Jurkiewicz, Dorota [1 ]
Jezela-Stanek, Aleksandra [1 ]
Ciara, Elzbieta [1 ]
Piekutowska-Abramczuk, Dorota [1 ]
Kugaudo, Monika [1 ]
Gajdulewicz, Maria [1 ]
Chrzanowska, Krystyna [1 ]
Popowska, Ewa [1 ]
Krajewska-Walasek, Malgorzata [1 ]
机构
[1] Childrens Mem Hlth Inst, Dept Med Genet, PL-04730 Warsaw, Poland
关键词
Coffin-Lowry syndrome; CLS females; RSK2; mutations; MLPA; X-chromosome inactivation; X-CHROMOSOME INACTIVATION; GENE RPS6KA3; CATAPLEXY;
D O I
10.1016/j.ejmg.2010.07.006
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Coffin-Lowry syndrome (CLS) is an X-linked semi-dominant disorder caused by mutations in the RSK2 gene and characterized by moderate to severe mental retardation, characteristic facial features, skeletal deformities, and tapering fingers in males. Females are usually much more mildly and variably affected thus more difficult to diagnose. In this study, molecular genetic analysis was carried out in four female patients presenting features of Coffin-Lowry syndrome. The probands were sporadic cases with no affected males in their families. The molecular analysis of the RSK2 gene revealed four novel mutations, including two frameshift and one missense mutation identified by sequencing, and one large deletion detected by multiplex ligation-dependent probe amplification (MLPA) analysis. Females exhibited a random X-chromosome inactivation pattern. To our knowledge, this is the first report of applying MLPA in the diagnostics of CLS and the first description of a large deletion in a CLS female. These results support including screening for large rearragements in the genetic analysis of female CLS patients. (C) 2010 Elsevier Masson SAS. All rights reserved.
引用
收藏
页码:268 / 273
页数:6
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