Identification of a novel recessive RELN mutation using a homozygous balanced reciprocal translocation

Maha Zaki, Marwa Shehab, Alice Kamal Abd El Aleem, Ghada Abdel-Salam, Hajira B. Koeller, Yesim Ilkin, M. Elizabeth Ross, William B. Dobyns, Joseph G. Gleeson

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

Two siblings from a consanguineous Egyptian marriage showed an identical phenotype of cortical lissencephaly with cerebellar hypoplasia, severe epilepsy, and mental retardation. Examination of karyotype revealed 46, t(7;12) (q22;p13)mat (7;12)(q22;p13)pat in both affected children, suggesting a homozygous reciprocal balanced translocation. Each healthy parent was a carrier of the balanced translocation in the heterozygous state, suggesting homozygous disruption of a gene involved in brain development. There were early spontaneous abortions in this family, as would be expected from transmission of an unbalanced chromosome. A disruption of RELN at 7q22.1 with absence of encoded protein was identified. This is the first demonstration that such rare homozygous translocations can be used to identify recessive disease gene mutations.

Original languageEnglish
Pages (from-to)939-944
Number of pages6
JournalAmerican Journal of Medical Genetics, Part A
Volume143
Issue number9
DOIs
Publication statusPublished - 1 May 2007
Externally publishedYes

Fingerprint

Lissencephaly
Recessive Genes
Spontaneous Abortion
Marriage
Karyotype
Intellectual Disability
Siblings
Epilepsy
Chromosomes
Phenotype
Mutation
Brain
Genes
Proteins
Cerebellar Hypoplasia

Keywords

  • Balanced translocation
  • Consanguinity
  • Homozygous
  • Lissencephaly
  • Reelin

ASJC Scopus subject areas

  • Genetics(clinical)

Cite this

Identification of a novel recessive RELN mutation using a homozygous balanced reciprocal translocation. / Zaki, Maha; Shehab, Marwa; Kamal Abd El Aleem, Alice; Abdel-Salam, Ghada; Koeller, Hajira B.; Ilkin, Yesim; Ross, M. Elizabeth; Dobyns, William B.; Gleeson, Joseph G.

In: American Journal of Medical Genetics, Part A, Vol. 143, No. 9, 01.05.2007, p. 939-944.

Research output: Contribution to journalArticle

Zaki, Maha ; Shehab, Marwa ; Kamal Abd El Aleem, Alice ; Abdel-Salam, Ghada ; Koeller, Hajira B. ; Ilkin, Yesim ; Ross, M. Elizabeth ; Dobyns, William B. ; Gleeson, Joseph G. / Identification of a novel recessive RELN mutation using a homozygous balanced reciprocal translocation. In: American Journal of Medical Genetics, Part A. 2007 ; Vol. 143, No. 9. pp. 939-944.
@article{b13bcb7abde645fb9821501afb4840f2,
title = "Identification of a novel recessive RELN mutation using a homozygous balanced reciprocal translocation",
abstract = "Two siblings from a consanguineous Egyptian marriage showed an identical phenotype of cortical lissencephaly with cerebellar hypoplasia, severe epilepsy, and mental retardation. Examination of karyotype revealed 46, t(7;12) (q22;p13)mat (7;12)(q22;p13)pat in both affected children, suggesting a homozygous reciprocal balanced translocation. Each healthy parent was a carrier of the balanced translocation in the heterozygous state, suggesting homozygous disruption of a gene involved in brain development. There were early spontaneous abortions in this family, as would be expected from transmission of an unbalanced chromosome. A disruption of RELN at 7q22.1 with absence of encoded protein was identified. This is the first demonstration that such rare homozygous translocations can be used to identify recessive disease gene mutations.",
keywords = "Balanced translocation, Consanguinity, Homozygous, Lissencephaly, Reelin",
author = "Maha Zaki and Marwa Shehab and {Kamal Abd El Aleem}, Alice and Ghada Abdel-Salam and Koeller, {Hajira B.} and Yesim Ilkin and Ross, {M. Elizabeth} and Dobyns, {William B.} and Gleeson, {Joseph G.}",
year = "2007",
month = "5",
day = "1",
doi = "10.1002/ajmg.a.31667",
language = "English",
volume = "143",
pages = "939--944",
journal = "American Journal of Medical Genetics, Part A",
issn = "1552-4825",
publisher = "Wiley-Liss Inc.",
number = "9",

}

TY - JOUR

T1 - Identification of a novel recessive RELN mutation using a homozygous balanced reciprocal translocation

AU - Zaki, Maha

AU - Shehab, Marwa

AU - Kamal Abd El Aleem, Alice

AU - Abdel-Salam, Ghada

AU - Koeller, Hajira B.

AU - Ilkin, Yesim

AU - Ross, M. Elizabeth

AU - Dobyns, William B.

AU - Gleeson, Joseph G.

PY - 2007/5/1

Y1 - 2007/5/1

N2 - Two siblings from a consanguineous Egyptian marriage showed an identical phenotype of cortical lissencephaly with cerebellar hypoplasia, severe epilepsy, and mental retardation. Examination of karyotype revealed 46, t(7;12) (q22;p13)mat (7;12)(q22;p13)pat in both affected children, suggesting a homozygous reciprocal balanced translocation. Each healthy parent was a carrier of the balanced translocation in the heterozygous state, suggesting homozygous disruption of a gene involved in brain development. There were early spontaneous abortions in this family, as would be expected from transmission of an unbalanced chromosome. A disruption of RELN at 7q22.1 with absence of encoded protein was identified. This is the first demonstration that such rare homozygous translocations can be used to identify recessive disease gene mutations.

AB - Two siblings from a consanguineous Egyptian marriage showed an identical phenotype of cortical lissencephaly with cerebellar hypoplasia, severe epilepsy, and mental retardation. Examination of karyotype revealed 46, t(7;12) (q22;p13)mat (7;12)(q22;p13)pat in both affected children, suggesting a homozygous reciprocal balanced translocation. Each healthy parent was a carrier of the balanced translocation in the heterozygous state, suggesting homozygous disruption of a gene involved in brain development. There were early spontaneous abortions in this family, as would be expected from transmission of an unbalanced chromosome. A disruption of RELN at 7q22.1 with absence of encoded protein was identified. This is the first demonstration that such rare homozygous translocations can be used to identify recessive disease gene mutations.

KW - Balanced translocation

KW - Consanguinity

KW - Homozygous

KW - Lissencephaly

KW - Reelin

UR - http://www.scopus.com/inward/record.url?scp=34247892266&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34247892266&partnerID=8YFLogxK

U2 - 10.1002/ajmg.a.31667

DO - 10.1002/ajmg.a.31667

M3 - Article

C2 - 17431900

AN - SCOPUS:34247892266

VL - 143

SP - 939

EP - 944

JO - American Journal of Medical Genetics, Part A

JF - American Journal of Medical Genetics, Part A

SN - 1552-4825

IS - 9

ER -