Case Report: De novo Variants of KMT2E Cause O'Donnell-Luria-Rodan Syndrome: Additional Cases and Literature Review
Introduction: O'Donnell-Luria-Rodan syndrome was recently identified as an autosomal dominant systemic disorder caused by variants in KMT2E. It is characterized by global developmental delay, some patients also exhibit autism, seizures, hypotonia, and/or feeding difficulties.Methods: Whole-exom...
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Frontiers Media S.A.
2021-02-01
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fped.2021.641841/full |
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| author | Yang Li Yang Li Lijuan Fan Rong Luo Zuozhen Yang Meng Yuan Meng Yuan Jinxiu Zhang Jinxiu Zhang Jing Gan Jing Gan |
| author_facet | Yang Li Yang Li Lijuan Fan Rong Luo Zuozhen Yang Meng Yuan Meng Yuan Jinxiu Zhang Jinxiu Zhang Jing Gan Jing Gan |
| author_sort | Yang Li |
| collection | DOAJ |
| description | Introduction: O'Donnell-Luria-Rodan syndrome was recently identified as an autosomal dominant systemic disorder caused by variants in KMT2E. It is characterized by global developmental delay, some patients also exhibit autism, seizures, hypotonia, and/or feeding difficulties.Methods: Whole-exome sequencing of family trios were performed for two independent children with unexplained recurrent seizures and developmental delay. Both cases were identified as having de novo variants in KMT2E. We also collected and summarized the clinical data and diagnosed them with O'Donnell-Luria-Rodan syndrome. Structural-prediction programs were used to draw the variants' locations.Results: A 186 G>A synonymous variant [NM_182931.3:exon4: c.186G>A (p.Ala62=)] was found in one family, resulting in alternative splicing acid. A 5417 C>T transition variant [NM_182931.3:exon27: c.5417C>T (p.Pro1806Leu)] was found in another family, resulting in 1806 Pro-to-Leu substitution. Both variants were classified as likely pathogenic according to the ACMG (American College of Medical Genetics and Genomics) guidelines and verified by Sanger sequencing.Conclusion: To date, three studies of O'Donnell-Luria-Rodan syndrome have been reported with heterogeneous clinical manifestations. As a newly recognized inherited systemic disorder, O'Donnell-Luria-Rodan syndrome needs to be paid more attention, especially in gene testing. |
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| series | Frontiers in Pediatrics |
| spelling | doaj.art-fd81aa558244436db5d367ef25c45f442022-12-21T17:00:57ZengFrontiers Media S.A.Frontiers in Pediatrics2296-23602021-02-01910.3389/fped.2021.641841641841Case Report: De novo Variants of KMT2E Cause O'Donnell-Luria-Rodan Syndrome: Additional Cases and Literature ReviewYang Li0Yang Li1Lijuan Fan2Rong Luo3Zuozhen Yang4Meng Yuan5Meng Yuan6Jinxiu Zhang7Jinxiu Zhang8Jing Gan9Jing Gan10Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, ChinaKey Laboratory of Obstetrics & Gynecologic and Pediatric Diseases and Birth Defects of the Ministry of Education, Sichuan University, Chengdu, ChinaDepartment of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, ChinaDepartment of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, ChinaCipher Gene LLC, Beijing, ChinaDepartment of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, ChinaKey Laboratory of Obstetrics & Gynecologic and Pediatric Diseases and Birth Defects of the Ministry of Education, Sichuan University, Chengdu, ChinaDepartment of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, ChinaKey Laboratory of Obstetrics & Gynecologic and Pediatric Diseases and Birth Defects of the Ministry of Education, Sichuan University, Chengdu, ChinaDepartment of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, ChinaKey Laboratory of Obstetrics & Gynecologic and Pediatric Diseases and Birth Defects of the Ministry of Education, Sichuan University, Chengdu, ChinaIntroduction: O'Donnell-Luria-Rodan syndrome was recently identified as an autosomal dominant systemic disorder caused by variants in KMT2E. It is characterized by global developmental delay, some patients also exhibit autism, seizures, hypotonia, and/or feeding difficulties.Methods: Whole-exome sequencing of family trios were performed for two independent children with unexplained recurrent seizures and developmental delay. Both cases were identified as having de novo variants in KMT2E. We also collected and summarized the clinical data and diagnosed them with O'Donnell-Luria-Rodan syndrome. Structural-prediction programs were used to draw the variants' locations.Results: A 186 G>A synonymous variant [NM_182931.3:exon4: c.186G>A (p.Ala62=)] was found in one family, resulting in alternative splicing acid. A 5417 C>T transition variant [NM_182931.3:exon27: c.5417C>T (p.Pro1806Leu)] was found in another family, resulting in 1806 Pro-to-Leu substitution. Both variants were classified as likely pathogenic according to the ACMG (American College of Medical Genetics and Genomics) guidelines and verified by Sanger sequencing.Conclusion: To date, three studies of O'Donnell-Luria-Rodan syndrome have been reported with heterogeneous clinical manifestations. As a newly recognized inherited systemic disorder, O'Donnell-Luria-Rodan syndrome needs to be paid more attention, especially in gene testing.https://www.frontiersin.org/articles/10.3389/fped.2021.641841/fullKMT2EO'Donnell-Luria-Rodan syndromeepilepsywhole-exome sequencingneurodevelopmental disorder |
| spellingShingle | Yang Li Yang Li Lijuan Fan Rong Luo Zuozhen Yang Meng Yuan Meng Yuan Jinxiu Zhang Jinxiu Zhang Jing Gan Jing Gan Case Report: De novo Variants of KMT2E Cause O'Donnell-Luria-Rodan Syndrome: Additional Cases and Literature Review Frontiers in Pediatrics KMT2E O'Donnell-Luria-Rodan syndrome epilepsy whole-exome sequencing neurodevelopmental disorder |
| title | Case Report: De novo Variants of KMT2E Cause O'Donnell-Luria-Rodan Syndrome: Additional Cases and Literature Review |
| title_full | Case Report: De novo Variants of KMT2E Cause O'Donnell-Luria-Rodan Syndrome: Additional Cases and Literature Review |
| title_fullStr | Case Report: De novo Variants of KMT2E Cause O'Donnell-Luria-Rodan Syndrome: Additional Cases and Literature Review |
| title_full_unstemmed | Case Report: De novo Variants of KMT2E Cause O'Donnell-Luria-Rodan Syndrome: Additional Cases and Literature Review |
| title_short | Case Report: De novo Variants of KMT2E Cause O'Donnell-Luria-Rodan Syndrome: Additional Cases and Literature Review |
| title_sort | case report de novo variants of kmt2e cause o donnell luria rodan syndrome additional cases and literature review |
| topic | KMT2E O'Donnell-Luria-Rodan syndrome epilepsy whole-exome sequencing neurodevelopmental disorder |
| url | https://www.frontiersin.org/articles/10.3389/fped.2021.641841/full |
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