Three de novo variants in KMT2A (MLL) identified by whole exome sequencing in patients with Wiedemann–Steiner syndrome
Abstract Background Wiedemann–Steiner syndrome (WSS) is an autosomal dominant disorder characterized by short stature, hypertrichosis, intellectual disability, developmental delay, along with facial dysmorphism. WSS patients exhibit great phenotypic heterogeneities. Some variants in KMT2A (MLL) gene...
Guardado en:
| Autores principales: | , , , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Wiley
2021
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/23f9593cea6343a8b9422c1d8eac532a |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:23f9593cea6343a8b9422c1d8eac532a |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:23f9593cea6343a8b9422c1d8eac532a2021-11-10T16:39:24ZThree de novo variants in KMT2A (MLL) identified by whole exome sequencing in patients with Wiedemann–Steiner syndrome2324-926910.1002/mgg3.1798https://doaj.org/article/23f9593cea6343a8b9422c1d8eac532a2021-10-01T00:00:00Zhttps://doi.org/10.1002/mgg3.1798https://doaj.org/toc/2324-9269Abstract Background Wiedemann–Steiner syndrome (WSS) is an autosomal dominant disorder characterized by short stature, hypertrichosis, intellectual disability, developmental delay, along with facial dysmorphism. WSS patients exhibit great phenotypic heterogeneities. Some variants in KMT2A (MLL) gene have been identified as the cause of WSS. Methods Whole exome sequencing on the probands followed by Sanger sequencing validations in the family were applied to determine genetic variants. In silico analyses were used for predicting potential effects of the variants. Results We identified three novel de novo heterozygous variants: c.883A>T (p.Lys295*), c.4171C>T (p.Gln1391*), and c.3499T>C (p.Cys1167Arg), in KMT2A gene from three unrelated Chinese WSS patients. According to the American College of Medical Genetics and Genomics (ACMG) guidelines, these three variants were classified as pathogenic, pathogenic and likely pathogenic variant, respectively. By reviewing all the available cases with same mutated KMT2A regions as the three patients had, we found that in addition to the representative symptoms, our patients exhibited some sporadically observed symptoms, such as severe ophthalmological symptoms, endocardial fibroelastosis, cytomegalovirus infection, and feet eversion. We also revealed that variants in different KMT2A regions contribute to the phenotypic heterogeneity of WSS, highlighting challenges in the diagnosis of syndromic disorders spanning a broad phenotypic spectrum. Conclusion Our study would aid in further broadening our knowledge about the genotype–phenotype correlation of WSS.Sukun LuoBo BiWenqian ZhangRui ZhouWei ChenPeiwei ZhaoYufeng HuangLi YuanXuelian HeWileyarticlede novo variantendocardial fibroelastosisKMT2Aneurodevelopment delayWiedemann–Steiner syndromeGeneticsQH426-470ENMolecular Genetics & Genomic Medicine, Vol 9, Iss 10, Pp n/a-n/a (2021) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
de novo variant endocardial fibroelastosis KMT2A neurodevelopment delay Wiedemann–Steiner syndrome Genetics QH426-470 |
| spellingShingle |
de novo variant endocardial fibroelastosis KMT2A neurodevelopment delay Wiedemann–Steiner syndrome Genetics QH426-470 Sukun Luo Bo Bi Wenqian Zhang Rui Zhou Wei Chen Peiwei Zhao Yufeng Huang Li Yuan Xuelian He Three de novo variants in KMT2A (MLL) identified by whole exome sequencing in patients with Wiedemann–Steiner syndrome |
| description |
Abstract Background Wiedemann–Steiner syndrome (WSS) is an autosomal dominant disorder characterized by short stature, hypertrichosis, intellectual disability, developmental delay, along with facial dysmorphism. WSS patients exhibit great phenotypic heterogeneities. Some variants in KMT2A (MLL) gene have been identified as the cause of WSS. Methods Whole exome sequencing on the probands followed by Sanger sequencing validations in the family were applied to determine genetic variants. In silico analyses were used for predicting potential effects of the variants. Results We identified three novel de novo heterozygous variants: c.883A>T (p.Lys295*), c.4171C>T (p.Gln1391*), and c.3499T>C (p.Cys1167Arg), in KMT2A gene from three unrelated Chinese WSS patients. According to the American College of Medical Genetics and Genomics (ACMG) guidelines, these three variants were classified as pathogenic, pathogenic and likely pathogenic variant, respectively. By reviewing all the available cases with same mutated KMT2A regions as the three patients had, we found that in addition to the representative symptoms, our patients exhibited some sporadically observed symptoms, such as severe ophthalmological symptoms, endocardial fibroelastosis, cytomegalovirus infection, and feet eversion. We also revealed that variants in different KMT2A regions contribute to the phenotypic heterogeneity of WSS, highlighting challenges in the diagnosis of syndromic disorders spanning a broad phenotypic spectrum. Conclusion Our study would aid in further broadening our knowledge about the genotype–phenotype correlation of WSS. |
| format |
article |
| author |
Sukun Luo Bo Bi Wenqian Zhang Rui Zhou Wei Chen Peiwei Zhao Yufeng Huang Li Yuan Xuelian He |
| author_facet |
Sukun Luo Bo Bi Wenqian Zhang Rui Zhou Wei Chen Peiwei Zhao Yufeng Huang Li Yuan Xuelian He |
| author_sort |
Sukun Luo |
| title |
Three de novo variants in KMT2A (MLL) identified by whole exome sequencing in patients with Wiedemann–Steiner syndrome |
| title_short |
Three de novo variants in KMT2A (MLL) identified by whole exome sequencing in patients with Wiedemann–Steiner syndrome |
| title_full |
Three de novo variants in KMT2A (MLL) identified by whole exome sequencing in patients with Wiedemann–Steiner syndrome |
| title_fullStr |
Three de novo variants in KMT2A (MLL) identified by whole exome sequencing in patients with Wiedemann–Steiner syndrome |
| title_full_unstemmed |
Three de novo variants in KMT2A (MLL) identified by whole exome sequencing in patients with Wiedemann–Steiner syndrome |
| title_sort |
three de novo variants in kmt2a (mll) identified by whole exome sequencing in patients with wiedemann–steiner syndrome |
| publisher |
Wiley |
| publishDate |
2021 |
| url |
https://doaj.org/article/23f9593cea6343a8b9422c1d8eac532a |
| work_keys_str_mv |
AT sukunluo threedenovovariantsinkmt2amllidentifiedbywholeexomesequencinginpatientswithwiedemannsteinersyndrome AT bobi threedenovovariantsinkmt2amllidentifiedbywholeexomesequencinginpatientswithwiedemannsteinersyndrome AT wenqianzhang threedenovovariantsinkmt2amllidentifiedbywholeexomesequencinginpatientswithwiedemannsteinersyndrome AT ruizhou threedenovovariantsinkmt2amllidentifiedbywholeexomesequencinginpatientswithwiedemannsteinersyndrome AT weichen threedenovovariantsinkmt2amllidentifiedbywholeexomesequencinginpatientswithwiedemannsteinersyndrome AT peiweizhao threedenovovariantsinkmt2amllidentifiedbywholeexomesequencinginpatientswithwiedemannsteinersyndrome AT yufenghuang threedenovovariantsinkmt2amllidentifiedbywholeexomesequencinginpatientswithwiedemannsteinersyndrome AT liyuan threedenovovariantsinkmt2amllidentifiedbywholeexomesequencinginpatientswithwiedemannsteinersyndrome AT xuelianhe threedenovovariantsinkmt2amllidentifiedbywholeexomesequencinginpatientswithwiedemannsteinersyndrome |
| _version_ |
1718439851875893248 |