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Title: A familial {open_quotes}balanced{close_quotes} 3;9 translocation with cryptic 8q insertion leading to deletion and duplication of 9p23 loci in siblings

Abstract

Families in which a balanced translocation has been transmitted from a normal parent to a child with a phenotypic abnormality have been a longstanding puzzle for human geneticists. A child with phenotypic features of the 9p- syndrome, including metopic craniosynostosis, small ears, abdominal wall defect, and mental retardation, was found to have a cytogenetically balanced 3;9 translocation, with breakpoints at 3p11 and 9p23, inherited from his normal father. He also exhibited marked hypopigmentation of hair and skin. Analysis with a cDNA probe from the TYRP1 (tyrosinase-related protein 1) gene in 9p23 showed heterozygous deletion in the child but in neither parent. This submicroscopic deletion also included loci D9S157, D9S274, D9S268, and D9S267. FISH analysis of the proband`s father indicated the 9p23 loci deleted in his son were present on neither the der(3) nor the der(9) translocation product, but had been inserted into the long arm of chromosome 8. Therefore, the apparent deletion of these loci in the proband was the result of meiotic segregation of the father`s 3;9 translocation chromosomes together with his normal chromosome 8. Neither the deletion from the translocation chromosomes nor the insertion into 8q was detectable by standard chromosome banding techniques. The proband`s sister exhibited speechmore » delay, mild facial dysmorphism, and renal malformation, and her karyotype was 46,XX. Molecular analysis of this sister showed 3 copies of 9p23 sequences, indicating that she had inherited normal chromosomes 3 and 9 from her father as well as the chromosome 8 with the insertion from 9p23. This analysis illustrates a new mechanism to explain cases of phenotypic discordance in familial balanced translocations: submicroscopic deletion of material from the translocation breakpoint and insertion into a third chromosome in the balanced parent, with meiotic segregation leading to loss of the inserted material in the child.« less

Authors:
;  [1]
  1. Children`s Hospital and Harvard Medical School, Boston, MA (United States)
Publication Date:
OSTI Identifier:
133778
Report Number(s):
CONF-941009-
Journal ID: AJHGAG; ISSN 0002-9297; TRN: 95:005313-0511
Resource Type:
Journal Article
Journal Name:
American Journal of Human Genetics
Additional Journal Information:
Journal Volume: 55; Journal Issue: Suppl.3; Conference: 44. annual meeting of the American Society of Human Genetics, Montreal (Canada), 18-22 Oct 1994; Other Information: PBD: Sep 1994
Country of Publication:
United States
Language:
English
Subject:
55 BIOLOGY AND MEDICINE, BASIC STUDIES; HUMAN CHROMOSOME 3; CHROMOSOMAL ABERRATIONS; SEGREGATION; HUMAN CHROMOSOME 9; PATIENTS; PHENOTYPE; HEREDITARY DISEASES; CONGENITAL MALFORMATIONS; MENTAL DISORDERS; HUMAN CHROMOSOME 8; FLUORESCENCE; DNA HYBRIDIZATION; PROBES; GENETICS; GENES; MEIOSIS

Citation Formats

Wagstaff, J, and Hemann, M. A familial {open_quotes}balanced{close_quotes} 3;9 translocation with cryptic 8q insertion leading to deletion and duplication of 9p23 loci in siblings. United States: N. p., 1994. Web.
Wagstaff, J, & Hemann, M. A familial {open_quotes}balanced{close_quotes} 3;9 translocation with cryptic 8q insertion leading to deletion and duplication of 9p23 loci in siblings. United States.
Wagstaff, J, and Hemann, M. 1994. "A familial {open_quotes}balanced{close_quotes} 3;9 translocation with cryptic 8q insertion leading to deletion and duplication of 9p23 loci in siblings". United States.
@article{osti_133778,
title = {A familial {open_quotes}balanced{close_quotes} 3;9 translocation with cryptic 8q insertion leading to deletion and duplication of 9p23 loci in siblings},
author = {Wagstaff, J and Hemann, M},
abstractNote = {Families in which a balanced translocation has been transmitted from a normal parent to a child with a phenotypic abnormality have been a longstanding puzzle for human geneticists. A child with phenotypic features of the 9p- syndrome, including metopic craniosynostosis, small ears, abdominal wall defect, and mental retardation, was found to have a cytogenetically balanced 3;9 translocation, with breakpoints at 3p11 and 9p23, inherited from his normal father. He also exhibited marked hypopigmentation of hair and skin. Analysis with a cDNA probe from the TYRP1 (tyrosinase-related protein 1) gene in 9p23 showed heterozygous deletion in the child but in neither parent. This submicroscopic deletion also included loci D9S157, D9S274, D9S268, and D9S267. FISH analysis of the proband`s father indicated the 9p23 loci deleted in his son were present on neither the der(3) nor the der(9) translocation product, but had been inserted into the long arm of chromosome 8. Therefore, the apparent deletion of these loci in the proband was the result of meiotic segregation of the father`s 3;9 translocation chromosomes together with his normal chromosome 8. Neither the deletion from the translocation chromosomes nor the insertion into 8q was detectable by standard chromosome banding techniques. The proband`s sister exhibited speech delay, mild facial dysmorphism, and renal malformation, and her karyotype was 46,XX. Molecular analysis of this sister showed 3 copies of 9p23 sequences, indicating that she had inherited normal chromosomes 3 and 9 from her father as well as the chromosome 8 with the insertion from 9p23. This analysis illustrates a new mechanism to explain cases of phenotypic discordance in familial balanced translocations: submicroscopic deletion of material from the translocation breakpoint and insertion into a third chromosome in the balanced parent, with meiotic segregation leading to loss of the inserted material in the child.},
doi = {},
url = {https://www.osti.gov/biblio/133778}, journal = {American Journal of Human Genetics},
number = Suppl.3,
volume = 55,
place = {United States},
year = {Thu Sep 01 00:00:00 EDT 1994},
month = {Thu Sep 01 00:00:00 EDT 1994}
}