Molecular characterization of a patient with central nervous system dysmyelination and cryptic unbalanced translocation between chromosomes 4q and 18q

Shelly R. Gunn, Mansoor Mohammed, Xavier T. Reveles, David H. Viskochil, Janice C. Palumbos, Teresa L. Johnson-Pais, Daniel Hale, Jack L. Lancaster, L. Jean Hardies, Odile Boespflug-Tanguy, Jannine D. Cody, Robin J. Leach

Research output: Contribution to journalArticle

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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 locusspecific 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.

Original languageEnglish (US)
Pages (from-to)127-135
Number of pages9
JournalAmerican Journal of Medical Genetics
Volume120 A
Issue number1
StatePublished - Jul 1 2003

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Comparative Genomic Hybridization
Central Nervous System
Chromosomes
Cytogenetic Analysis
Genes
Foot Deformities
Ear Canal
Karyotype
Hearing Loss
Chromosome Aberrations
Pathologic Constriction
Genome

All Science Journal Classification (ASJC) codes

  • Genetics(clinical)

Cite this

Gunn, S. R., Mohammed, M., Reveles, X. T., Viskochil, D. H., Palumbos, J. C., Johnson-Pais, T. L., ... Leach, R. J. (2003). Molecular characterization of a patient with central nervous system dysmyelination and cryptic unbalanced translocation between chromosomes 4q and 18q. American Journal of Medical Genetics, 120 A(1), 127-135.
Gunn, Shelly R. ; Mohammed, Mansoor ; Reveles, Xavier T. ; Viskochil, David H. ; Palumbos, Janice C. ; Johnson-Pais, Teresa L. ; Hale, Daniel ; Lancaster, Jack L. ; Hardies, L. Jean ; Boespflug-Tanguy, Odile ; Cody, Jannine D. ; Leach, Robin J. / Molecular characterization of a patient with central nervous system dysmyelination and cryptic unbalanced translocation between chromosomes 4q and 18q. In: American Journal of Medical Genetics. 2003 ; Vol. 120 A, No. 1. pp. 127-135.
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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 locusspecific 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.",
author = "Gunn, {Shelly R.} and Mansoor Mohammed and Reveles, {Xavier T.} and Viskochil, {David H.} and Palumbos, {Janice C.} and Johnson-Pais, {Teresa L.} and Daniel Hale and Lancaster, {Jack L.} and Hardies, {L. Jean} and Odile Boespflug-Tanguy and Cody, {Jannine D.} and Leach, {Robin J.}",
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Gunn, SR, Mohammed, M, Reveles, XT, Viskochil, DH, Palumbos, JC, Johnson-Pais, TL, Hale, D, Lancaster, JL, Hardies, LJ, Boespflug-Tanguy, O, Cody, JD & Leach, RJ 2003, 'Molecular characterization of a patient with central nervous system dysmyelination and cryptic unbalanced translocation between chromosomes 4q and 18q', American Journal of Medical Genetics, vol. 120 A, no. 1, pp. 127-135.

Molecular characterization of a patient with central nervous system dysmyelination and cryptic unbalanced translocation between chromosomes 4q and 18q. / Gunn, Shelly R.; Mohammed, Mansoor; Reveles, Xavier T.; Viskochil, David H.; Palumbos, Janice C.; Johnson-Pais, Teresa L.; Hale, Daniel; Lancaster, Jack L.; Hardies, L. Jean; Boespflug-Tanguy, Odile; Cody, Jannine D.; Leach, Robin J.

In: American Journal of Medical Genetics, Vol. 120 A, No. 1, 01.07.2003, p. 127-135.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Molecular characterization of a patient with central nervous system dysmyelination and cryptic unbalanced translocation between chromosomes 4q and 18q

AU - Gunn, Shelly R.

AU - Mohammed, Mansoor

AU - Reveles, Xavier T.

AU - Viskochil, David H.

AU - Palumbos, Janice C.

AU - Johnson-Pais, Teresa L.

AU - Hale, Daniel

AU - Lancaster, Jack L.

AU - Hardies, L. Jean

AU - Boespflug-Tanguy, Odile

AU - Cody, Jannine D.

AU - Leach, Robin J.

PY - 2003/7/1

Y1 - 2003/7/1

N2 - 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 locusspecific 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.

AB - 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 locusspecific 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.

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EP - 135

JO - American Journal of Medical Genetics, Part A

JF - American Journal of Medical Genetics, Part A

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