A novel frameshift variant of GATA3 (p.Ala17ProfsTer178) responsible for HDR syndrome in a Japanese family
HDR syndrome is an autosomal dominant disorder characterized by hypoparathyroidism (H), deafness (D), and renal dysplasia (R) caused by genetic variants of the GATA3 gene. We present the case of a 38-year-old Japanese man with HDR syndrome who exhibited hypoparathyroidism, sensorineural deafness, re...
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| Format: | Article |
| Language: | English |
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The Japan Endocrine Society
2024-11-01
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| Series: | Endocrine Journal |
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| Online Access: | https://www.jstage.jst.go.jp/article/endocrj/71/11/71_EJ24-0147/_html/-char/en |
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| author | Yutaka Hasegawa Toshie Segawa Ai Chida Eriko Yoshida Hirofumi Kinno Hiraku Chiba Tomoyasu Oda Yoshihiko Takahashi Koji Nata Yasushi Ishigaki |
| author_facet | Yutaka Hasegawa Toshie Segawa Ai Chida Eriko Yoshida Hirofumi Kinno Hiraku Chiba Tomoyasu Oda Yoshihiko Takahashi Koji Nata Yasushi Ishigaki |
| author_sort | Yutaka Hasegawa |
| collection | DOAJ |
| description | HDR syndrome is an autosomal dominant disorder characterized by hypoparathyroidism (H), deafness (D), and renal dysplasia (R) caused by genetic variants of the GATA3 gene. We present the case of a 38-year-old Japanese man with HDR syndrome who exhibited hypoparathyroidism, sensorineural deafness, renal dysfunction, severe symptomatic hypocalcemia with Chvostek’s and Trousseau’s signs, and QT prolongation on electrocardiography. He had a family history of deafness and hypocalcemia. Genetic testing revealed a novel GATA3 gene variant at exon 2 (c.48delC), which induces a frameshift resulting in termination at codon 178, causing HDR syndrome. We summarized 45 Japanese cases of HDR syndrome with regard to the mode of onset (familial or sporadic) and the age at diagnosis. In addition, we summarized all previous cases of HDR syndrome with GATA3 gene variants. Mapping of previously reported genetic variants in HDR syndrome revealed that most missense variants were observed at exons 4 and 5 regions in the GATA3 gene. These two regions contain zinc finger domains, demonstrating their functional importance in GATA3 transcription. This review of literature provides a useful reference for diagnosing HDR syndrome and predicting the related future manifestations. |
| format | Article |
| id | doaj-art-67707815315240189128bb6481d72575 |
| institution | Kabale University |
| issn | 1348-4540 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | The Japan Endocrine Society |
| record_format | Article |
| series | Endocrine Journal |
| spelling | doaj-art-67707815315240189128bb6481d725752025-01-22T05:38:18ZengThe Japan Endocrine SocietyEndocrine Journal1348-45402024-11-0171111077108610.1507/endocrj.EJ24-0147endocrjA novel frameshift variant of GATA3 (p.Ala17ProfsTer178) responsible for HDR syndrome in a Japanese familyYutaka Hasegawa0Toshie Segawa1Ai Chida2Eriko Yoshida3Hirofumi Kinno4Hiraku Chiba5Tomoyasu Oda6Yoshihiko Takahashi7Koji Nata8Yasushi Ishigaki9Division of Diabetes, Metabolism and Endocrinology, Department of Internal Medicine, Iwate Medical University, Iwate 028-3695, JapanDivision of Diabetes, Metabolism and Endocrinology, Department of Internal Medicine, Iwate Medical University, Iwate 028-3695, JapanDivision of Diabetes, Metabolism and Endocrinology, Department of Internal Medicine, Iwate Medical University, Iwate 028-3695, JapanDivision of Diabetes, Metabolism and Endocrinology, Department of Internal Medicine, Iwate Medical University, Iwate 028-3695, JapanDivision of Diabetes, Metabolism and Endocrinology, Department of Internal Medicine, Iwate Medical University, Iwate 028-3695, JapanDivision of Diabetes, Metabolism and Endocrinology, Department of Internal Medicine, Iwate Medical University, Iwate 028-3695, JapanDivision of Diabetes, Metabolism and Endocrinology, Department of Internal Medicine, Iwate Medical University, Iwate 028-3695, JapanDivision of Diabetes, Metabolism and Endocrinology, Department of Internal Medicine, Iwate Medical University, Iwate 028-3695, JapanDivision of Medical Biochemistry, School of Pharmacy, Iwate Medical University, Iwate 028-3694, JapanDivision of Diabetes, Metabolism and Endocrinology, Department of Internal Medicine, Iwate Medical University, Iwate 028-3695, JapanHDR syndrome is an autosomal dominant disorder characterized by hypoparathyroidism (H), deafness (D), and renal dysplasia (R) caused by genetic variants of the GATA3 gene. We present the case of a 38-year-old Japanese man with HDR syndrome who exhibited hypoparathyroidism, sensorineural deafness, renal dysfunction, severe symptomatic hypocalcemia with Chvostek’s and Trousseau’s signs, and QT prolongation on electrocardiography. He had a family history of deafness and hypocalcemia. Genetic testing revealed a novel GATA3 gene variant at exon 2 (c.48delC), which induces a frameshift resulting in termination at codon 178, causing HDR syndrome. We summarized 45 Japanese cases of HDR syndrome with regard to the mode of onset (familial or sporadic) and the age at diagnosis. In addition, we summarized all previous cases of HDR syndrome with GATA3 gene variants. Mapping of previously reported genetic variants in HDR syndrome revealed that most missense variants were observed at exons 4 and 5 regions in the GATA3 gene. These two regions contain zinc finger domains, demonstrating their functional importance in GATA3 transcription. This review of literature provides a useful reference for diagnosing HDR syndrome and predicting the related future manifestations.https://www.jstage.jst.go.jp/article/endocrj/71/11/71_EJ24-0147/_html/-char/enhypoparathyroidismdeafness and renal dysplasia (hdr) syndromegata3 |
| spellingShingle | Yutaka Hasegawa Toshie Segawa Ai Chida Eriko Yoshida Hirofumi Kinno Hiraku Chiba Tomoyasu Oda Yoshihiko Takahashi Koji Nata Yasushi Ishigaki A novel frameshift variant of GATA3 (p.Ala17ProfsTer178) responsible for HDR syndrome in a Japanese family Endocrine Journal hypoparathyroidism deafness and renal dysplasia (hdr) syndrome gata3 |
| title | A novel frameshift variant of GATA3 (p.Ala17ProfsTer178) responsible for HDR syndrome in a Japanese family |
| title_full | A novel frameshift variant of GATA3 (p.Ala17ProfsTer178) responsible for HDR syndrome in a Japanese family |
| title_fullStr | A novel frameshift variant of GATA3 (p.Ala17ProfsTer178) responsible for HDR syndrome in a Japanese family |
| title_full_unstemmed | A novel frameshift variant of GATA3 (p.Ala17ProfsTer178) responsible for HDR syndrome in a Japanese family |
| title_short | A novel frameshift variant of GATA3 (p.Ala17ProfsTer178) responsible for HDR syndrome in a Japanese family |
| title_sort | novel frameshift variant of gata3 p ala17profster178 responsible for hdr syndrome in a japanese family |
| topic | hypoparathyroidism deafness and renal dysplasia (hdr) syndrome gata3 |
| url | https://www.jstage.jst.go.jp/article/endocrj/71/11/71_EJ24-0147/_html/-char/en |
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