Genotype-phenotype correlation of deletions and duplications of 4p: case reports and literature review
Structural rearrangements of chromosome 4p gives rise to a group of rare genomic disorders that mainly result in two different clinical entities: Wolf-Hirschhorn syndrome (WHS) and partial 4p trisomy. The severity of the phenotype depends on the size of the deletion or locus duplication. Here, we pr...
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Frontiers Media S.A.
2023-06-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2023.1174314/full |
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| author | Xuan Zhang Hongjuan Lu Hanran Yang Yichen Ji Huixin Liu Wenjian Liu Jiayi Li Zhixian Yang Wei Sun |
| author_facet | Xuan Zhang Hongjuan Lu Hanran Yang Yichen Ji Huixin Liu Wenjian Liu Jiayi Li Zhixian Yang Wei Sun |
| author_sort | Xuan Zhang |
| collection | DOAJ |
| description | Structural rearrangements of chromosome 4p gives rise to a group of rare genomic disorders that mainly result in two different clinical entities: Wolf-Hirschhorn syndrome (WHS) and partial 4p trisomy. The severity of the phenotype depends on the size of the deletion or locus duplication. Here, we present two unrelated individuals with a copy number variation of chromosome 4p. Inverted duplication deletions (inv dup-del) in 4p are particularly rare. Case 1 describes a 15-year-old girl with a 1.055 Mb deletion of terminal 4p, distal to the recognized critical region of WHS, and a large duplication of 9.6 Mb in size from 4p16.3 to p16.1. She had postnatal development delay, intellectual disability (especially pronounced in speech), seizure/electroencephalogram anomalies, and facial dysmorphic features. This unusual chromosomal imbalance resulted in the WHS phenotype rather than the 4p trisomy syndrome phenotype. Case 2 describes a 21-month-old boy with a 1.386 Mb terminal 4p deletion who presented with slight developmental delay, borderline intellectual disability, and seizures. Combined with previous reported cases of 4 pter del-dup or pure 4p terminal deletions, our observations suggest that terminal chromosome 4p deletion is more pathogenic than the concomitant partial 4p duplication, and some regions of the 4p terminal may have regulatory effects on the remaining region of 4p. About nine cases have been reported thus far to date, and our study delineates further genotype-phenotype correlations about terminal 4p duplication-deletions for predicting disease prognosis and patient counseling. |
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| last_indexed | 2024-03-13T05:38:55Z |
| publishDate | 2023-06-01 |
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| spelling | doaj.art-c1a1d895c4674dd68e2c571ea21ee03f2023-06-14T04:46:39ZengFrontiers Media S.A.Frontiers in Genetics1664-80212023-06-011410.3389/fgene.2023.11743141174314Genotype-phenotype correlation of deletions and duplications of 4p: case reports and literature reviewXuan Zhang0Hongjuan Lu1Hanran Yang2Yichen JiHuixin Liu3Wenjian Liu4Jiayi Li5Zhixian Yang6Wei Sun7Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, ChinaDepartment of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, ChinaDepartment of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, ChinaDepartment of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, ChinaDepartment of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, ChinaDepartment of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, ChinaDepartment of Pediatrics, Peking University First Hospital, Beijing, ChinaDepartment of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, ChinaStructural rearrangements of chromosome 4p gives rise to a group of rare genomic disorders that mainly result in two different clinical entities: Wolf-Hirschhorn syndrome (WHS) and partial 4p trisomy. The severity of the phenotype depends on the size of the deletion or locus duplication. Here, we present two unrelated individuals with a copy number variation of chromosome 4p. Inverted duplication deletions (inv dup-del) in 4p are particularly rare. Case 1 describes a 15-year-old girl with a 1.055 Mb deletion of terminal 4p, distal to the recognized critical region of WHS, and a large duplication of 9.6 Mb in size from 4p16.3 to p16.1. She had postnatal development delay, intellectual disability (especially pronounced in speech), seizure/electroencephalogram anomalies, and facial dysmorphic features. This unusual chromosomal imbalance resulted in the WHS phenotype rather than the 4p trisomy syndrome phenotype. Case 2 describes a 21-month-old boy with a 1.386 Mb terminal 4p deletion who presented with slight developmental delay, borderline intellectual disability, and seizures. Combined with previous reported cases of 4 pter del-dup or pure 4p terminal deletions, our observations suggest that terminal chromosome 4p deletion is more pathogenic than the concomitant partial 4p duplication, and some regions of the 4p terminal may have regulatory effects on the remaining region of 4p. About nine cases have been reported thus far to date, and our study delineates further genotype-phenotype correlations about terminal 4p duplication-deletions for predicting disease prognosis and patient counseling.https://www.frontiersin.org/articles/10.3389/fgene.2023.1174314/fullchromosome 4pterminal 4p deletionwolf-Hirschhorn syndromepartial duplication 4p4p trisomy |
| spellingShingle | Xuan Zhang Hongjuan Lu Hanran Yang Yichen Ji Huixin Liu Wenjian Liu Jiayi Li Zhixian Yang Wei Sun Genotype-phenotype correlation of deletions and duplications of 4p: case reports and literature review Frontiers in Genetics chromosome 4p terminal 4p deletion wolf-Hirschhorn syndrome partial duplication 4p 4p trisomy |
| title | Genotype-phenotype correlation of deletions and duplications of 4p: case reports and literature review |
| title_full | Genotype-phenotype correlation of deletions and duplications of 4p: case reports and literature review |
| title_fullStr | Genotype-phenotype correlation of deletions and duplications of 4p: case reports and literature review |
| title_full_unstemmed | Genotype-phenotype correlation of deletions and duplications of 4p: case reports and literature review |
| title_short | Genotype-phenotype correlation of deletions and duplications of 4p: case reports and literature review |
| title_sort | genotype phenotype correlation of deletions and duplications of 4p case reports and literature review |
| topic | chromosome 4p terminal 4p deletion wolf-Hirschhorn syndrome partial duplication 4p 4p trisomy |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2023.1174314/full |
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