Genetic investigations of autosomal recessive inherited ichthyosis impressed by fetal ultrasound: Exome sequencing and haplotype linkage analysis
Objective: Ichthyosis are complex skin diseases, characterized by hyperkeratosis with various degrees of thickening, desquamation, and erythema. The prenatal diagnosis of ichthyosis is challenged due to the clinical and genetic heterogeneity and the late-onset of fetal features on ultrasound scan. H...
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Elsevier
2025-01-01
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| Series: | Taiwanese Journal of Obstetrics & Gynecology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1028455924002778 |
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| author | Ting-Yu Chang Zhu Wei Lim Yi-Tzu Chu Wan-Ju Wu Mei-Hui Lee Shun-Ping Chang Dong-Jay Lee Wen-Hsiang Lin Ming Ho Jin-Chung Shih Gwo-Chin Ma Ming Chen |
| author_facet | Ting-Yu Chang Zhu Wei Lim Yi-Tzu Chu Wan-Ju Wu Mei-Hui Lee Shun-Ping Chang Dong-Jay Lee Wen-Hsiang Lin Ming Ho Jin-Chung Shih Gwo-Chin Ma Ming Chen |
| author_sort | Ting-Yu Chang |
| collection | DOAJ |
| description | Objective: Ichthyosis are complex skin diseases, characterized by hyperkeratosis with various degrees of thickening, desquamation, and erythema. The prenatal diagnosis of ichthyosis is challenged due to the clinical and genetic heterogeneity and the late-onset of fetal features on ultrasound scan. Here, we reported two fetuses with Harlequin ichthyosis (HI), a severe subtype of autosomal recessive congenital ichthyosis (ARCI), who were diagnosed prenatally by images and genetic investigations. Preimplantation genetic testing (PGT) was also performed in one case and the family to prevent the transmission of this condition. Materials and methods: Fetal images were analyzed by detailed fetal ultrasound. Genetic defects in affected fetuses were detected using whole exome sequencing (WES) and confirmed by Sanger sequencing. PGT for monogenic disease (PGT-M) was performed using short tandem repeat (STR) markers and amplification refractory mutation system quantitative polymerase chain reaction (ARMS-qPCR). Results: WES identified pathogenic mutations in ABCA12 gene in both fetuses. Genome Analysis ToolKit (GATK 4 version 4.2.1.0) was merged using a setting of the trio model for exome variation analysis. Confirmatory Sanger sequencing of ABCA12 gene was also applied to both parents. Disease-cause haplotyping by STR markers and ARMS-qPCR for PGT-M strategy were conducted in family 1. Linkage analysis in conjunction with STR was used in the first case, whereas unequal coverage of WES was deciphered with the inspiration of the second case a few years later. Both cases were diagnosed by high coverage WES and led to successful subsequent pregnancies by preimplantation genetic diagnosis and genetic amniocentesis. Conclusion: Preimplantation genetic testing using STR linkage analysis can rescue cases with autosomal recessive inheritance when only one mutation is found in the putative gene, while reanalysis of high-coverage WES by optimized updated bioinformatics should always be considered in addition to whole genome sequencing. |
| format | Article |
| id | doaj-art-fd6f0105a62a4e5f9506f52b8732e844 |
| institution | Kabale University |
| issn | 1028-4559 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
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| series | Taiwanese Journal of Obstetrics & Gynecology |
| spelling | doaj-art-fd6f0105a62a4e5f9506f52b8732e8442025-01-09T06:12:50ZengElsevierTaiwanese Journal of Obstetrics & Gynecology1028-45592025-01-016415360Genetic investigations of autosomal recessive inherited ichthyosis impressed by fetal ultrasound: Exome sequencing and haplotype linkage analysisTing-Yu Chang0Zhu Wei Lim1Yi-Tzu Chu2Wan-Ju Wu3Mei-Hui Lee4Shun-Ping Chang5Dong-Jay Lee6Wen-Hsiang Lin7Ming Ho8Jin-Chung Shih9Gwo-Chin Ma10Ming Chen11Department of Genomic Medicine and Center for Medical Genetics, Changhua Christian Hospital, Changhua, Taiwan; Department of Bioscience Technology, Chung Yuan Christian University, Taoyuan, TaiwanDepartment of Obstetrics and Gynecology, Changhua Christian Hospital, Changhua, TaiwanDepartment of Obstetrics and Gynecology, Changhua Christian Hospital, Changhua, TaiwanDepartment of Genomic Medicine and Center for Medical Genetics, Changhua Christian Hospital, Changhua, Taiwan; Department of Obstetrics and Gynecology, Changhua Christian Hospital, Changhua, TaiwanDepartment of Genomic Medicine and Center for Medical Genetics, Changhua Christian Hospital, Changhua, TaiwanDepartment of Genomic Medicine and Center for Medical Genetics, Changhua Christian Hospital, Changhua, TaiwanDepartment of Medical Research, Changhua Christian Hospital, Changhua, TaiwanWelgene Biotechnology Company, Nangang Business Park, Taipei, TaiwanDepartment of Obstetrics and Gynecology, China Medical University Hospital, Taichung, TaiwanDepartment of Obstetrics and Gynecology, College of Medicine, National Taiwan University, Taipei, TaiwanDepartment of Genomic Medicine and Center for Medical Genetics, Changhua Christian Hospital, Changhua, Taiwan; Department of Medical Research, Changhua Christian Hospital, Changhua, Taiwan; Department of Medical Laboratory Science and Biotechnology, Central Taiwan University of Science and Technology, Taichung, Taiwan; Corresponding author. Department of Genomic Medicine and Center for Medical Genetics, Changhua Christian Hospital, Changhua, Taiwan.Department of Genomic Medicine and Center for Medical Genetics, Changhua Christian Hospital, Changhua, Taiwan; Department of Obstetrics and Gynecology, Changhua Christian Hospital, Changhua, Taiwan; Department of Medical Research, Changhua Christian Hospital, Changhua, Taiwan; Department of Obstetrics and Gynecology, College of Medicine, National Taiwan University, Taipei, Taiwan; Department of Medical Genetics, National Taiwan University Hospital, Taipei, Taiwan; Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan; Department of Medical Sciences, National Tsing Hua University, Hsinchu, Taiwan; Corresponding author. Department of Genomic Medicine and Center for Medical Genetics, Changhua Christian Hospital, Changhua, Taiwan.Objective: Ichthyosis are complex skin diseases, characterized by hyperkeratosis with various degrees of thickening, desquamation, and erythema. The prenatal diagnosis of ichthyosis is challenged due to the clinical and genetic heterogeneity and the late-onset of fetal features on ultrasound scan. Here, we reported two fetuses with Harlequin ichthyosis (HI), a severe subtype of autosomal recessive congenital ichthyosis (ARCI), who were diagnosed prenatally by images and genetic investigations. Preimplantation genetic testing (PGT) was also performed in one case and the family to prevent the transmission of this condition. Materials and methods: Fetal images were analyzed by detailed fetal ultrasound. Genetic defects in affected fetuses were detected using whole exome sequencing (WES) and confirmed by Sanger sequencing. PGT for monogenic disease (PGT-M) was performed using short tandem repeat (STR) markers and amplification refractory mutation system quantitative polymerase chain reaction (ARMS-qPCR). Results: WES identified pathogenic mutations in ABCA12 gene in both fetuses. Genome Analysis ToolKit (GATK 4 version 4.2.1.0) was merged using a setting of the trio model for exome variation analysis. Confirmatory Sanger sequencing of ABCA12 gene was also applied to both parents. Disease-cause haplotyping by STR markers and ARMS-qPCR for PGT-M strategy were conducted in family 1. Linkage analysis in conjunction with STR was used in the first case, whereas unequal coverage of WES was deciphered with the inspiration of the second case a few years later. Both cases were diagnosed by high coverage WES and led to successful subsequent pregnancies by preimplantation genetic diagnosis and genetic amniocentesis. Conclusion: Preimplantation genetic testing using STR linkage analysis can rescue cases with autosomal recessive inheritance when only one mutation is found in the putative gene, while reanalysis of high-coverage WES by optimized updated bioinformatics should always be considered in addition to whole genome sequencing.http://www.sciencedirect.com/science/article/pii/S1028455924002778Harlequin ichthyosisABCA12WESLinkage analysisUnequal coverage |
| spellingShingle | Ting-Yu Chang Zhu Wei Lim Yi-Tzu Chu Wan-Ju Wu Mei-Hui Lee Shun-Ping Chang Dong-Jay Lee Wen-Hsiang Lin Ming Ho Jin-Chung Shih Gwo-Chin Ma Ming Chen Genetic investigations of autosomal recessive inherited ichthyosis impressed by fetal ultrasound: Exome sequencing and haplotype linkage analysis Taiwanese Journal of Obstetrics & Gynecology Harlequin ichthyosis ABCA12 WES Linkage analysis Unequal coverage |
| title | Genetic investigations of autosomal recessive inherited ichthyosis impressed by fetal ultrasound: Exome sequencing and haplotype linkage analysis |
| title_full | Genetic investigations of autosomal recessive inherited ichthyosis impressed by fetal ultrasound: Exome sequencing and haplotype linkage analysis |
| title_fullStr | Genetic investigations of autosomal recessive inherited ichthyosis impressed by fetal ultrasound: Exome sequencing and haplotype linkage analysis |
| title_full_unstemmed | Genetic investigations of autosomal recessive inherited ichthyosis impressed by fetal ultrasound: Exome sequencing and haplotype linkage analysis |
| title_short | Genetic investigations of autosomal recessive inherited ichthyosis impressed by fetal ultrasound: Exome sequencing and haplotype linkage analysis |
| title_sort | genetic investigations of autosomal recessive inherited ichthyosis impressed by fetal ultrasound exome sequencing and haplotype linkage analysis |
| topic | Harlequin ichthyosis ABCA12 WES Linkage analysis Unequal coverage |
| url | http://www.sciencedirect.com/science/article/pii/S1028455924002778 |
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