Detection of low-level somatic and germline mosaicism by denaturing high-performance liquid chromatography in a EURO-MRX family with SLC6A8 deficiency

被引:28
作者
Betsalel, Ofir T. [1 ]
van de Kamp, Jiddeke M. [2 ]
Martinez-Munoz, Cristina [1 ]
Rosenberg, Efraim H. [1 ]
de Brouwer, Arjan P. M. [5 ,6 ]
Pouwels, Petra J. W. [3 ]
van der Knaap, Marjo S. [4 ]
Mancini, Grazia M. S. [7 ]
Jakobs, Cornelis [1 ]
Hamel, Ben C. J. [5 ,6 ]
Salomons, Gajja S. [1 ]
机构
[1] Vrije Univ Amsterdam, Med Ctr, Dept Clin Chem, Metabol Unit PK1x009, NL-1081 HV Amsterdam, Netherlands
[2] Vrije Univ Amsterdam, Med Ctr, Dept Clin Genet, Amsterdam, Netherlands
[3] Vrije Univ Amsterdam, Med Ctr, Dept Phys & Med Technol, Amsterdam, Netherlands
[4] Vrije Univ Amsterdam, Med Ctr, Dept Child Neurol, Amsterdam, Netherlands
[5] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6525 ED Nijmegen, Netherlands
[6] EURO MRX Consortium, Nijmegen, Netherlands
[7] Erasmus Univ MC, Sophia Childrens Hosp, Dept Clin Genet, Rotterdam, Netherlands
关键词
creatine transporter deficiency; SLC6A8; X-linked mental retardation; DHPLC; low-level somatic mosaicism; germline mosaicism;
D O I
10.1007/s10048-008-0125-5
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Creatine transporter deficiency is an X-linked mental retardation disorder caused by mutations in the creatine transporter gene, SLC6A8. In a European Mental Retardation Consortium panel of 66 patients, we identified a male with mental retardation, caused by a c.1059_1061delCTT; p.Phe354del mutation in the SLC6A8 gene. With the use of direct DNA sequencing, the mutation was also found in the brother of the proband, but not in their mother. However, by analyzing EDTA blood of the mother with denaturing high-performance liquid chromatography (DHPLC), we could show that the mother displays low-level somatic mosaicism for the three base-pair deletion. This study indicates DHPLC as an important tool in the detection of low-level mosaicism, as does it illustrate the importance of considering somatic and germline mosaicism in the case of apparent de novo mutation.
引用
收藏
页码:183 / 190
页数:8
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