title: Molecular characterization of a patient with central nervous system dysmyelination and cryptic unbalanced translocation between chromosomes 4q and 18q.
abstract: We report on a 12-year-old boy who presented with delayed development and CNS dysmyelination. Genetic studies showed a normal 46,XY karyotype by routine cytogenetic analysis, and 46,XY.ish del(18)(q23)(D18Z1+, MBP-) by FISH using a locus-specific probe for the MBP gene (18q23). Though the patient appeared to have normal chromosome 18s by repeated high resolution banding analysis, his clinical features were suggestive of a deletion of 18q. These included hearing loss secondary to stenosis of the external auditory canals, abnormal facial features, and foot deformities. FISH studies with genomic probes from 18q22.3 to 18qter confirmed a cryptic deletion which encompassed the MBP gene. In an attempt to further characterize the deletion, whole genome screening was conducted using array based comparative genomic hybridization (array CGH) analysis. The array CGH data not only confirmed a cryptic deletion in the 18q22.3 to 18qter region of approximately 7 Mb, it also showed a previously undetected 3.7 Mb gain of 4q material. FISH studies demonstrated that the gained 4q material was translocated distal to the 18qter deletion breakpoint. The 18q deletion contains, in addition to MBP, other known genes including CYB5, ZNF236, GALR1, and NFATC1, while the gained 4q material includes the genes FACL1 and 2, KLKB1, F11 and MTNR1A. The use of these combined methodologies has resulted in the first reported case in which array CGH has been used to characterize a congenital chromosomal abnormality, highlighting the need for innovative molecular cytogenetic techniques in the diagnosis of patients with idiopathic neurological abnormalities.
authors.affiliation: Department of Cellular and Structural Biology, The University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA. Gunn@UTHSCSA.edu
authors.forename: Shelly R
authors.initials: SR
authors.lastname: Gunn
authors.forename: Mansoor
authors.initials: M
authors.lastname: Mohammed
authors.forename: Xavier T
authors.initials: XT
authors.lastname: Reveles
authors.forename: David H
authors.initials: DH
authors.lastname: Viskochil
authors.forename: Janice C
authors.initials: JC
authors.lastname: Palumbos
authors.forename: Teresa L
authors.initials: TL
authors.lastname: Johnson-Pais
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Hale
authors.forename: Jack L
authors.initials: JL
authors.lastname: Lancaster
authors.forename: L Jean
authors.initials: LJ
authors.lastname: Hardies
authors.forename: Odile
authors.initials: O
authors.lastname: Boespflug-Tanguy
authors.forename: Jannine D
authors.initials: JD
authors.lastname: Cody
authors.forename: Robin J
authors.initials: RJ
authors.lastname: Leach
mesh_terms: D002490:Central Nervous System / Q000002:abnormalities*; D002648:Child; D002871:Chromosome Banding; D002887:Chromosomes, Human, Pair 18; D002894:Chromosomes, Human, Pair 4; D003582:Cytogenetics; D004247:DNA / Q000737:chemistry; D017353:Gene Deletion; D005838:Genotype; D034381:Hearing Loss / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008607:Intellectual Disability / Q000235:genetics; D007621:Karyotyping; D008279:Magnetic Resonance Imaging; D008297:Male; D008957:Models, Genetic; D004676:Myelin Basic Protein / Q000235:genetics; D009186:Myelin Sheath / Q000737:chemistry*; D009693:Nucleic Acid Hybridization; D014178:Translocation, Genetic
chemical_list: D004676:Myelin Basic Protein; D004247:DNA