Case Report: Contiguous Xq22.3 Deletion Associated with ATS-ID Syndrome: From Genotype to Further Delineation of the Phenotype
Alport syndrome with intellectual disability (ATS-ID, AMME complex; OMIM #300194) is an X-linked contiguous gene deletion syndrome associated with an Xq22.3 locus mainly characterized by hematuria, renal failure, hearing loss/deafness, neurodevelopmental disorder (NDD), midface retrusion, and ellipt...
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Frontiers Media S.A.
2021-10-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2021.750110/full |
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| author | Jan Smetana Vladimira Vallova Vladimira Vallova Marketa Wayhelova Marketa Wayhelova Eva Hladilkova Hana Filkova Vera Horinova Petr Broz Aneta Mikulasova Renata Gaillyova Petr Kuglík Petr Kuglík |
| author_facet | Jan Smetana Vladimira Vallova Vladimira Vallova Marketa Wayhelova Marketa Wayhelova Eva Hladilkova Hana Filkova Vera Horinova Petr Broz Aneta Mikulasova Renata Gaillyova Petr Kuglík Petr Kuglík |
| author_sort | Jan Smetana |
| collection | DOAJ |
| description | Alport syndrome with intellectual disability (ATS-ID, AMME complex; OMIM #300194) is an X-linked contiguous gene deletion syndrome associated with an Xq22.3 locus mainly characterized by hematuria, renal failure, hearing loss/deafness, neurodevelopmental disorder (NDD), midface retrusion, and elliptocytosis. It is thought that ATS-ID is caused by the loss of function of COL4A5 (ATS) and FACL4 (ACSL4) genes through the interstitial (micro)deletion of chromosomal band Xq22.3. We report detailed phenotypic description and results from genome-wide screening of a Czech family with diagnosis ATS-ID (proband, maternal uncle, and two female carriers). Female carriers showed mild clinical features of microscopic hematuria only, while affected males displayed several novel clinical features associated with ATS-ID. Utilization of whole-exome sequencing discovered the presence of approximately 3 Mb of deletion in the Xq23 area, which affected 19 genes from TSC22D3 to CHRDL1. We compared the clinical phenotype with previously reported three ATS-ID families worldwide and correlated their clinical manifestations with the incidence of genes in both telomeric and centromeric regions of the deleted chromosomal area. In addition to previously described phenotypes associated with aberrations in AMMECR1 and FACL4, we identified two genes, members of tripartite motif family MID2 and subunit of the proteasome PA700/19S complex (PSMD10), respectively, as prime candidate genes responsible for additional clinical features observed in our patients with ATS-ID. Overall, our findings further improve the knowledge about the clinical impact of Xq23 deletions and bring novel information about phenotype/genotype association of this chromosomal aberration. |
| first_indexed | 2024-12-17T12:42:31Z |
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| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-12-17T12:42:31Z |
| publishDate | 2021-10-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Genetics |
| spelling | doaj.art-553c39dc21554bb8bf291f2161880eb22022-12-21T21:47:54ZengFrontiers Media S.A.Frontiers in Genetics1664-80212021-10-011210.3389/fgene.2021.750110750110Case Report: Contiguous Xq22.3 Deletion Associated with ATS-ID Syndrome: From Genotype to Further Delineation of the PhenotypeJan Smetana0Vladimira Vallova1Vladimira Vallova2Marketa Wayhelova3Marketa Wayhelova4Eva Hladilkova5Hana Filkova6Vera Horinova7Petr Broz8Aneta Mikulasova9Renata Gaillyova10Petr Kuglík11Petr Kuglík12Department of Genetics and Molecular Biology, Institute of Experimental Biology, Faculty of Science, Masaryk University, Brno, CzechDepartment of Genetics and Molecular Biology, Institute of Experimental Biology, Faculty of Science, Masaryk University, Brno, CzechDepartment of Medical Genetics and Genomics, University Hospital Brno, Brno, CzechDepartment of Genetics and Molecular Biology, Institute of Experimental Biology, Faculty of Science, Masaryk University, Brno, CzechDepartment of Medical Genetics and Genomics, University Hospital Brno, Brno, CzechDepartment of Medical Genetics and Genomics, University Hospital Brno, Brno, CzechDepartment of Medical Genetics and Genomics, University Hospital Brno, Brno, CzechGenetic Ambulance and Counseling, Jihlava, CzechDepartment of Biology and Medical Genetics, 2nd Faculty of Medicine, Charles University Prague and Faculty Hospital Motol, Prague, CzechBiosciences Institute, Newcastle University, Newcastle upon Tyne, United KingdomDepartment of Medical Genetics and Genomics, University Hospital Brno, Brno, CzechDepartment of Genetics and Molecular Biology, Institute of Experimental Biology, Faculty of Science, Masaryk University, Brno, CzechDepartment of Medical Genetics and Genomics, University Hospital Brno, Brno, CzechAlport syndrome with intellectual disability (ATS-ID, AMME complex; OMIM #300194) is an X-linked contiguous gene deletion syndrome associated with an Xq22.3 locus mainly characterized by hematuria, renal failure, hearing loss/deafness, neurodevelopmental disorder (NDD), midface retrusion, and elliptocytosis. It is thought that ATS-ID is caused by the loss of function of COL4A5 (ATS) and FACL4 (ACSL4) genes through the interstitial (micro)deletion of chromosomal band Xq22.3. We report detailed phenotypic description and results from genome-wide screening of a Czech family with diagnosis ATS-ID (proband, maternal uncle, and two female carriers). Female carriers showed mild clinical features of microscopic hematuria only, while affected males displayed several novel clinical features associated with ATS-ID. Utilization of whole-exome sequencing discovered the presence of approximately 3 Mb of deletion in the Xq23 area, which affected 19 genes from TSC22D3 to CHRDL1. We compared the clinical phenotype with previously reported three ATS-ID families worldwide and correlated their clinical manifestations with the incidence of genes in both telomeric and centromeric regions of the deleted chromosomal area. In addition to previously described phenotypes associated with aberrations in AMMECR1 and FACL4, we identified two genes, members of tripartite motif family MID2 and subunit of the proteasome PA700/19S complex (PSMD10), respectively, as prime candidate genes responsible for additional clinical features observed in our patients with ATS-ID. Overall, our findings further improve the knowledge about the clinical impact of Xq23 deletions and bring novel information about phenotype/genotype association of this chromosomal aberration.https://www.frontiersin.org/articles/10.3389/fgene.2021.750110/fullATS-MR syndrometrio-based whole exome sequencinggenotype-phenotype analysisneurodevelopmental disordersXq22.3q23 deletions |
| spellingShingle | Jan Smetana Vladimira Vallova Vladimira Vallova Marketa Wayhelova Marketa Wayhelova Eva Hladilkova Hana Filkova Vera Horinova Petr Broz Aneta Mikulasova Renata Gaillyova Petr Kuglík Petr Kuglík Case Report: Contiguous Xq22.3 Deletion Associated with ATS-ID Syndrome: From Genotype to Further Delineation of the Phenotype Frontiers in Genetics ATS-MR syndrome trio-based whole exome sequencing genotype-phenotype analysis neurodevelopmental disorders Xq22.3q23 deletions |
| title | Case Report: Contiguous Xq22.3 Deletion Associated with ATS-ID Syndrome: From Genotype to Further Delineation of the Phenotype |
| title_full | Case Report: Contiguous Xq22.3 Deletion Associated with ATS-ID Syndrome: From Genotype to Further Delineation of the Phenotype |
| title_fullStr | Case Report: Contiguous Xq22.3 Deletion Associated with ATS-ID Syndrome: From Genotype to Further Delineation of the Phenotype |
| title_full_unstemmed | Case Report: Contiguous Xq22.3 Deletion Associated with ATS-ID Syndrome: From Genotype to Further Delineation of the Phenotype |
| title_short | Case Report: Contiguous Xq22.3 Deletion Associated with ATS-ID Syndrome: From Genotype to Further Delineation of the Phenotype |
| title_sort | case report contiguous xq22 3 deletion associated with ats id syndrome from genotype to further delineation of the phenotype |
| topic | ATS-MR syndrome trio-based whole exome sequencing genotype-phenotype analysis neurodevelopmental disorders Xq22.3q23 deletions |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2021.750110/full |
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