title: Detection of low-level somatic and germline mosaicism by denaturing high-performance liquid chromatography in a EURO-MRX family with SLC6A8 deficiency.
abstract: 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.
authors: Department of Clinical Chemistry, VU University Medical Center, Amsterdam, The Netherlands.
authors: Ofir T
authors: OT
authors: Betsalel
authors: Jiddeke M
authors: JM
authors: van de Kamp
authors: Cristina
authors: C
authors: Martínez-Muñoz
authors: Efraim H
authors: EH
authors: Rosenberg
authors: Arjan P M
authors: AP
authors: de Brouwer
authors: Petra J W
authors: PJ
authors: Pouwels
authors: Marjo S
authors: MS
authors: van der Knaap
authors: Grazia M S
authors: GM
authors: Mancini
authors: Cornelis
authors: C
authors: Jakobs
authors: Ben C J
authors: BC
authors: Hamel
authors: Gajja S
authors: GS
authors: Salomons
mesh_terms: D000293:Adolescent; D000595:Amino Acid Sequence; D001483:Base Sequence; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000097:blood / Q000235:genetics; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D050172:Genes, X-Linked; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D038901:X-Linked Intellectual Disability / Q000097:blood / Q000235:genetics*; D008969:Molecular Sequence Data; D009030:Mosaicism; D009419:Nerve Tissue Proteins / Q000097:blood / Q000172:deficiency* / Q000235:genetics*; D009691:Nucleic Acid Denaturation; D010375:Pedigree; D050480:Plasma Membrane Neurotransmitter Transport Proteins / Q000097:blood / Q000172:deficiency* / Q000235:genetics*; D017384:Sequence Deletion; D017386:Sequence Homology, Amino Acid; D014162:Transfection
chemical_list: D009419:Nerve Tissue Proteins; D050480:Plasma Membrane Neurotransmitter Transport Proteins; C094770:SLC6A8 protein, human; D004247:DNA