Clinical features and genetic analysis of a family with t(5;9) (p15;p24) balanced translocation leading to Cri-du-chat syndrome in offspring

BackgroundBalanced translocations are common chromosomal structural abnormalities that usually do not involve a gain or loss of genetic material; and carriers usually display normal phenotypes and intelligence. However, unbalanced rearranged gametes can be produced during the meiotic division of rep...

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Main Authors: Jing Zhao, Ping Chen, Yijia Ren, Shurong Li, Weiyi Zhang, Yan Li, Fengyu Wang
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-05-01
Series:Frontiers in Genetics
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Online Access:https://www.frontiersin.org/articles/10.3389/fgene.2025.1550937/full
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author Jing Zhao
Ping Chen
Yijia Ren
Shurong Li
Weiyi Zhang
Yan Li
Fengyu Wang
author_facet Jing Zhao
Ping Chen
Yijia Ren
Shurong Li
Weiyi Zhang
Yan Li
Fengyu Wang
author_sort Jing Zhao
collection DOAJ
description BackgroundBalanced translocations are common chromosomal structural abnormalities that usually do not involve a gain or loss of genetic material; and carriers usually display normal phenotypes and intelligence. However, unbalanced rearranged gametes can be produced during the meiotic division of reproductive cells, leading to infertility, miscarriage, stillbirth, or the birth of newborns with malformations and chromosomal abnormalities. These adverse pregnancy outcomes create significant burdens for families and societies and affect the quality of life of newborns, threatening their health.ObjectiveIndividuals carrying balanced translocations can have phenotypically normal offspring, but they also face high risks of natural miscarriage and giving birth to newborns with chromosomal abnormalities. We characterized individual clinical features and conducted a genetic analysis of the members of a family with t (5; 9) (p15; p24) balanced translocation leading to Cri-du-chat syndrome in the offspring.Study designWe performed a chromosomal karyotyping with high-resolution G-banding on the proband and her family members to detect their chromosomal configurations. We also used chromosomal microarray analyses (CMA) to detect copy number variants. Enrichment analysis of genes in the duplicated or deleted regions of 5p and 9p was performed using Metascape. Results: The proband (III7), her father (II3), her brother (III5), and her cousin (III14) were all carriers of the t (5; 9) (p15; p24) balanced translocation. Offspring (IV5, IV7, IV9, and IV12) were affected. Genetic microarray results of IV7 showed a 26.3 Mb deletion on chromosome five and a 15.3 Mb duplication on chromosome 9. Genetic microarray results of IV5, IV9, and IV12 showed a 26.5 Mb duplication on chromosome five and a 15.4 Mb deletion on chromosome 9.ConclusionThis study reports a rare familial balanced translocation pedigree, particularly noting that the offspring can suffer from Cri-du-chat syndrome, which suggests a potential new genetic model for this syndrome. It provides novel insights for genetic counseling and prenatal diagnosis in patients with adverse pregnancy outcomes before attempting another pregnancy.
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spelling doaj-art-e03719814b2f4a8bbf6082abca4c66272025-08-20T02:14:22ZengFrontiers Media S.A.Frontiers in Genetics1664-80212025-05-011610.3389/fgene.2025.15509371550937Clinical features and genetic analysis of a family with t(5;9) (p15;p24) balanced translocation leading to Cri-du-chat syndrome in offspringJing Zhao0Ping Chen1Yijia Ren2Shurong Li3Weiyi Zhang4Yan Li5Fengyu Wang6Department of Obstetrics and Gynecology, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, Henan, ChinaDepartment of Obstetrics and Gynecology, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, Henan, ChinaZhengzhou KingMed Clinical Laboratory Co., Ltd, Zhengzhou, Henan, ChinaDepartment of Obstetrics and Gynecology, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, Henan, ChinaDepartment of Obstetrics and Gynecology, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, Henan, ChinaDepartment of Obstetrics and Gynecology, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, Henan, ChinaDepartment of Neurology, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, Zhengzhou, Henan, ChinaBackgroundBalanced translocations are common chromosomal structural abnormalities that usually do not involve a gain or loss of genetic material; and carriers usually display normal phenotypes and intelligence. However, unbalanced rearranged gametes can be produced during the meiotic division of reproductive cells, leading to infertility, miscarriage, stillbirth, or the birth of newborns with malformations and chromosomal abnormalities. These adverse pregnancy outcomes create significant burdens for families and societies and affect the quality of life of newborns, threatening their health.ObjectiveIndividuals carrying balanced translocations can have phenotypically normal offspring, but they also face high risks of natural miscarriage and giving birth to newborns with chromosomal abnormalities. We characterized individual clinical features and conducted a genetic analysis of the members of a family with t (5; 9) (p15; p24) balanced translocation leading to Cri-du-chat syndrome in the offspring.Study designWe performed a chromosomal karyotyping with high-resolution G-banding on the proband and her family members to detect their chromosomal configurations. We also used chromosomal microarray analyses (CMA) to detect copy number variants. Enrichment analysis of genes in the duplicated or deleted regions of 5p and 9p was performed using Metascape. Results: The proband (III7), her father (II3), her brother (III5), and her cousin (III14) were all carriers of the t (5; 9) (p15; p24) balanced translocation. Offspring (IV5, IV7, IV9, and IV12) were affected. Genetic microarray results of IV7 showed a 26.3 Mb deletion on chromosome five and a 15.3 Mb duplication on chromosome 9. Genetic microarray results of IV5, IV9, and IV12 showed a 26.5 Mb duplication on chromosome five and a 15.4 Mb deletion on chromosome 9.ConclusionThis study reports a rare familial balanced translocation pedigree, particularly noting that the offspring can suffer from Cri-du-chat syndrome, which suggests a potential new genetic model for this syndrome. It provides novel insights for genetic counseling and prenatal diagnosis in patients with adverse pregnancy outcomes before attempting another pregnancy.https://www.frontiersin.org/articles/10.3389/fgene.2025.1550937/fullbalanced translocation familycharacteristicsCri-du-chat syndromeprenatal diagnosisgenetic counseling
spellingShingle Jing Zhao
Ping Chen
Yijia Ren
Shurong Li
Weiyi Zhang
Yan Li
Fengyu Wang
Clinical features and genetic analysis of a family with t(5;9) (p15;p24) balanced translocation leading to Cri-du-chat syndrome in offspring
Frontiers in Genetics
balanced translocation family
characteristics
Cri-du-chat syndrome
prenatal diagnosis
genetic counseling
title Clinical features and genetic analysis of a family with t(5;9) (p15;p24) balanced translocation leading to Cri-du-chat syndrome in offspring
title_full Clinical features and genetic analysis of a family with t(5;9) (p15;p24) balanced translocation leading to Cri-du-chat syndrome in offspring
title_fullStr Clinical features and genetic analysis of a family with t(5;9) (p15;p24) balanced translocation leading to Cri-du-chat syndrome in offspring
title_full_unstemmed Clinical features and genetic analysis of a family with t(5;9) (p15;p24) balanced translocation leading to Cri-du-chat syndrome in offspring
title_short Clinical features and genetic analysis of a family with t(5;9) (p15;p24) balanced translocation leading to Cri-du-chat syndrome in offspring
title_sort clinical features and genetic analysis of a family with t 5 9 p15 p24 balanced translocation leading to cri du chat syndrome in offspring
topic balanced translocation family
characteristics
Cri-du-chat syndrome
prenatal diagnosis
genetic counseling
url https://www.frontiersin.org/articles/10.3389/fgene.2025.1550937/full
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