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Title: Prenatally diagnosed de novo apparently balanced complex chromosome rearrangements: Two new cases and review of the literature

Abstract

Complex chromosome rearrangements (CCR) are rare structural rearrangements. Currently six cases of prenatally diagnosed balanced de novo CCR have been described. We present two new cases of prenatally ascertained balanced de novo CCR. In the first case, an amniocentesis revealed a balanced de novo three-way CCR involving chromosomes 5,6, and 11 with a pericentric inversion of chromosome 5 [four breaks]. In the second case a balanced de novo rearrangement was identified by amniocentesis which involved a reciprocal translocation between chromosomes 3 and 8 and a CCR involving chromosomes 6,7, and 18 [six breaks]. The use of whole chromosome painting helped elucidate the nature of these rearrangements. A review of the postnatally ascertained cases suggests that most patients have congenital anomalies, minor anomalies, and/or developmental delay/mental retardation. In addition, there appears to be a relationship between the number of chromosome breaks and the extent of phenotypic effects. The paucity of information regarding prenatally diagnosed CCR and the bias of ascertainment of postnatal CCR cases poses a problem in counseling families. 38 refs., 3 figs., 4 tabs.

Authors:
; ;  [1]
  1. Bowman Gray School of Medicine of Wake Forest Univ., Winston-Salem, NC (United States) [and others
Publication Date:
OSTI Identifier:
539404
Resource Type:
Journal Article
Resource Relation:
Journal Name: American Journal of Medical Genetics; Journal Volume: 64; Journal Issue: 3; Other Information: PBD: 23 Aug 1996
Country of Publication:
United States
Language:
English
Subject:
55 BIOLOGY AND MEDICINE, BASIC STUDIES; CHROMOSOMAL ABERRATIONS; DETECTION; FETUSES; DIAGNOSIS; HUMAN CHROMOSOMES; CHROMOSOME BREAKAGE; PATIENTS; CONGENITAL MALFORMATIONS; MENTAL DISORDERS; PHENOTYPE; KARYOTYPE; HUMAN CHROMOSOME 3; HUMAN CHROMOSOME 8; HUMAN CHROMOSOME 5; HUMAN CHROMOSOME 6; HUMAN CHROMOSOME 7; HUMAN CHROMOSOME 18; BANDING TECHNIQUES

Citation Formats

Ruiz, C., Grubs, R.E., and Jewett, T. Prenatally diagnosed de novo apparently balanced complex chromosome rearrangements: Two new cases and review of the literature. United States: N. p., 1996. Web. doi:10.1002/(SICI)1096-8628(19960823)64:3<478::AID-AJMG6>3.3.CO;2-7.
Ruiz, C., Grubs, R.E., & Jewett, T. Prenatally diagnosed de novo apparently balanced complex chromosome rearrangements: Two new cases and review of the literature. United States. doi:10.1002/(SICI)1096-8628(19960823)64:3<478::AID-AJMG6>3.3.CO;2-7.
Ruiz, C., Grubs, R.E., and Jewett, T. Fri . "Prenatally diagnosed de novo apparently balanced complex chromosome rearrangements: Two new cases and review of the literature". United States. doi:10.1002/(SICI)1096-8628(19960823)64:3<478::AID-AJMG6>3.3.CO;2-7.
@article{osti_539404,
title = {Prenatally diagnosed de novo apparently balanced complex chromosome rearrangements: Two new cases and review of the literature},
author = {Ruiz, C. and Grubs, R.E. and Jewett, T.},
abstractNote = {Complex chromosome rearrangements (CCR) are rare structural rearrangements. Currently six cases of prenatally diagnosed balanced de novo CCR have been described. We present two new cases of prenatally ascertained balanced de novo CCR. In the first case, an amniocentesis revealed a balanced de novo three-way CCR involving chromosomes 5,6, and 11 with a pericentric inversion of chromosome 5 [four breaks]. In the second case a balanced de novo rearrangement was identified by amniocentesis which involved a reciprocal translocation between chromosomes 3 and 8 and a CCR involving chromosomes 6,7, and 18 [six breaks]. The use of whole chromosome painting helped elucidate the nature of these rearrangements. A review of the postnatally ascertained cases suggests that most patients have congenital anomalies, minor anomalies, and/or developmental delay/mental retardation. In addition, there appears to be a relationship between the number of chromosome breaks and the extent of phenotypic effects. The paucity of information regarding prenatally diagnosed CCR and the bias of ascertainment of postnatal CCR cases poses a problem in counseling families. 38 refs., 3 figs., 4 tabs.},
doi = {10.1002/(SICI)1096-8628(19960823)64:3<478::AID-AJMG6>3.3.CO;2-7},
journal = {American Journal of Medical Genetics},
number = 3,
volume = 64,
place = {United States},
year = {Fri Aug 23 00:00:00 EDT 1996},
month = {Fri Aug 23 00:00:00 EDT 1996}
}
  • Complex chromosome rearrangements (CCR) are rare structural rearrangements involving at least three chromosomes with three or more breakpoints. Although there have been numerous reports of individuals with CCR, most have been ascertained through the presence of multiple congenital anomalies, recurrent pregnancy loss, or infertility. Few cases have been ascertained prenatally. We present two new cases of prenatally ascertained CCR. In the first case, an amniocentesis revealed an apparently balanced de novo rearrangement in which chromosomes 5, 6 and 11 were involved in a three-way translocation: 46,XY,t(6;5)(5;11)(q23;p14.3;q15;p13). The pregnancy was unevenful. Recently, at the age of 9 months, a physical andmore » developmental evaluation were normal but, height, weight, and head circumference were below the 5th percentile. In the second case an amniocentesis revealed an unbalanced de novo rearrangement involving separate translocations and an interstitial deletion: 46,XY,del(6)(q25.3q27),t(3;8)(p13;q21.3),t(6;18)(p11.2;q11.2). A meconium plug was present at birth and at 6 months of age surgery for Hirschsprung`s disease was required. Currently, at 10 months of age, the patient has hypotonia and developmental delay. The paucity of information regarding prenatally diagnosed CCR poses a problem in counseling families. Of the four prenatally diagnosed balanced de novo CCR cases, three had abnormal outcomes. In a review of the literature, approximately 70% of the postnatally ascertained balanced de novo CCR cases were associated with congenital anomalies, growth retardation and/or mental retardation. More information regarding the outcome of prenatally ascertained balanced de novo CCR is required for accurate risk assessment.« less
  • Robertsonian translocations are usually ascertained through abnormal children, making proposed phenotypic effects of apparently balanced translocations difficult to study in an unbiased way. From molecular genetic studies, though, some apparently balanced rearrangments are now known to be associated with phenotypic abnormalities resulting from uniparental disomy. Molecular explanations for other cases in which abnormality is seen in a balanced translocation carrier are being sought. In the present paper, an infant is described who has retarded growth, developmental delay, gross muscular hypotonia, slender habitus, frontal bossing, micrognathia, hooked nose, abundant wispy hair, and blue sclerae. Cytogenetically, she appeared to be a carriermore » of a balanced, paternally derived 14;21 Robertsonian translocation. Analysis of DNA polymorphisms showed that she had no paternal allele at the D14S13 locus (14q32). Study of additional DNA markers within 14q32 revealed that her previously undescribed phenotype results from an interstitial microdeletion within 14q32. Fluorescent in situ hybridization was used to show that this microdeletion had occurred de novo on the Robertsonian translocation chromosome. These observations may reactivate old suspicions of a causal association between Robertsonian translocations and de novo rearrangements in offspring; a systematic search for similar subcytogentic rearrangements in other families, in which there are phenotypically abnormal children with apparently balanced translocations, may be fruitful. The clinical and molecular genetic data presented also define a new contiguous gene syndrome due to interstitial 14q32 deletion. 42 refs., 4 figs., 1 tab.« less
  • We report a new de novo case of a balanced whole-arm reciprocal translocation, detected at prenatal diagnosis for late maternal age. A review of previous cases indicates there is a risk of chromosomally abnormal liveborn offspring when a parent is a carrier of this type of translocation, particularly when the translocated region is a small chromosomal segment. Due to the limited number of cases, exact reproductive risks are not available. This is the second example of such a translocation of chromosomes 1 and 5, raising the possibility of nonrandom involvement of certain chromosomes in balanced nonacrocentric whole-arm reciprocal translocations. 18more » refs., 1 fig., 1 tab.« less
  • Craniosynostosis (CRS) is frequently seen in the del(7p) syndrome, and the gene for this cranial anomaly (CRS1) has been assigned to 7p21. The authors present a 3-year-old boy with CRS involving the sagittal and coronal sutures, who had a de novo and apparently balanced translocation, t(6;7)(q16.2;p15.3). Southern blot analysis of several loci on 7p14{yields}pter showed that the patient was heterozygous for HOX1I and IL6, possibly homozygous for D7S149, but hemizygous for D7S135 with a loss of the paternal allele. These findings suggest the localization of a candidate gene for CRS1 to be on 7p15.3 in the close proximity to themore » D7S135 locus. 19 refs., 5 figs., 2 tabs.« less
  • We report on a girl with Klippel-Feil anomaly, type A1 brachydactyly, and minor facial anomalies. She has an apparently balanced de novo reciprocal translocation between 5q11.2 and 17q23. The possible significance of this chromosomal abnormality is discussed. 7 refs., 3 figs.