Cargando…
De Novo variants in the KMT2A (MLL) gene causing atypical Wiedemann-Steiner syndrome in two unrelated individuals identified by clinical exome sequencing
BACKGROUND: Wiedemann-Steiner Syndrome (WSS) is characterized by short stature, a variety of dysmorphic facial and skeletal features, characteristic hypertrichosis cubiti (excessive hair on the elbows), mild-to-moderate developmental delay and intellectual disability. [MIM#: 605130]. Here we report...
Autores principales: | , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2014
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4072606/ https://www.ncbi.nlm.nih.gov/pubmed/24886118 http://dx.doi.org/10.1186/1471-2350-15-49 |
_version_ | 1782322990229225472 |
---|---|
author | Strom, Samuel P Lozano, Reymundo Lee, Hane Dorrani, Naghmeh Mann, John O’Lague, Patricia F Mans, Nicole Deignan, Joshua L Vilain, Eric Nelson, Stanley F Grody, Wayne W Quintero-Rivera, Fabiola |
author_facet | Strom, Samuel P Lozano, Reymundo Lee, Hane Dorrani, Naghmeh Mann, John O’Lague, Patricia F Mans, Nicole Deignan, Joshua L Vilain, Eric Nelson, Stanley F Grody, Wayne W Quintero-Rivera, Fabiola |
author_sort | Strom, Samuel P |
collection | PubMed |
description | BACKGROUND: Wiedemann-Steiner Syndrome (WSS) is characterized by short stature, a variety of dysmorphic facial and skeletal features, characteristic hypertrichosis cubiti (excessive hair on the elbows), mild-to-moderate developmental delay and intellectual disability. [MIM#: 605130]. Here we report two unrelated children for whom clinical exome sequencing of parent-proband trios was performed at UCLA, resulting in a molecular diagnosis of WSS and atypical clinical presentation. CASE PRESENTATION: For patient 1, clinical features at 9 years of age included developmental delay, craniofacial abnormalities, and multiple minor anomalies. Patient 2 presented at 1 year of age with developmental delay, microphthalmia, partial 3–4 left hand syndactyly, and craniofacial abnormalities. A de novo missense c.4342T>C variant and a de novo splice site c.4086+G>A variant were identified in the KMT2A gene in patients 1 and 2, respectively. CONCLUSIONS: Based on the clinical and molecular findings, both patients appear to have novel presentations of WSS. As the hallmark hypertrichosis cubiti was not initially appreciated in either case, this syndrome was not suspected during the clinical evaluation. This report expands the phenotypic spectrum of the clinical phenotypes and KMT2A variants associated with WSS. |
format | Online Article Text |
id | pubmed-4072606 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-40726062014-06-27 De Novo variants in the KMT2A (MLL) gene causing atypical Wiedemann-Steiner syndrome in two unrelated individuals identified by clinical exome sequencing Strom, Samuel P Lozano, Reymundo Lee, Hane Dorrani, Naghmeh Mann, John O’Lague, Patricia F Mans, Nicole Deignan, Joshua L Vilain, Eric Nelson, Stanley F Grody, Wayne W Quintero-Rivera, Fabiola BMC Med Genet Case Report BACKGROUND: Wiedemann-Steiner Syndrome (WSS) is characterized by short stature, a variety of dysmorphic facial and skeletal features, characteristic hypertrichosis cubiti (excessive hair on the elbows), mild-to-moderate developmental delay and intellectual disability. [MIM#: 605130]. Here we report two unrelated children for whom clinical exome sequencing of parent-proband trios was performed at UCLA, resulting in a molecular diagnosis of WSS and atypical clinical presentation. CASE PRESENTATION: For patient 1, clinical features at 9 years of age included developmental delay, craniofacial abnormalities, and multiple minor anomalies. Patient 2 presented at 1 year of age with developmental delay, microphthalmia, partial 3–4 left hand syndactyly, and craniofacial abnormalities. A de novo missense c.4342T>C variant and a de novo splice site c.4086+G>A variant were identified in the KMT2A gene in patients 1 and 2, respectively. CONCLUSIONS: Based on the clinical and molecular findings, both patients appear to have novel presentations of WSS. As the hallmark hypertrichosis cubiti was not initially appreciated in either case, this syndrome was not suspected during the clinical evaluation. This report expands the phenotypic spectrum of the clinical phenotypes and KMT2A variants associated with WSS. BioMed Central 2014-05-01 /pmc/articles/PMC4072606/ /pubmed/24886118 http://dx.doi.org/10.1186/1471-2350-15-49 Text en Copyright © 2014 Strom et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Case Report Strom, Samuel P Lozano, Reymundo Lee, Hane Dorrani, Naghmeh Mann, John O’Lague, Patricia F Mans, Nicole Deignan, Joshua L Vilain, Eric Nelson, Stanley F Grody, Wayne W Quintero-Rivera, Fabiola De Novo variants in the KMT2A (MLL) gene causing atypical Wiedemann-Steiner syndrome in two unrelated individuals identified by clinical exome sequencing |
title | De Novo variants in the KMT2A (MLL) gene causing atypical Wiedemann-Steiner syndrome in two unrelated individuals identified by clinical exome sequencing |
title_full | De Novo variants in the KMT2A (MLL) gene causing atypical Wiedemann-Steiner syndrome in two unrelated individuals identified by clinical exome sequencing |
title_fullStr | De Novo variants in the KMT2A (MLL) gene causing atypical Wiedemann-Steiner syndrome in two unrelated individuals identified by clinical exome sequencing |
title_full_unstemmed | De Novo variants in the KMT2A (MLL) gene causing atypical Wiedemann-Steiner syndrome in two unrelated individuals identified by clinical exome sequencing |
title_short | De Novo variants in the KMT2A (MLL) gene causing atypical Wiedemann-Steiner syndrome in two unrelated individuals identified by clinical exome sequencing |
title_sort | de novo variants in the kmt2a (mll) gene causing atypical wiedemann-steiner syndrome in two unrelated individuals identified by clinical exome sequencing |
topic | Case Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4072606/ https://www.ncbi.nlm.nih.gov/pubmed/24886118 http://dx.doi.org/10.1186/1471-2350-15-49 |
work_keys_str_mv | AT stromsamuelp denovovariantsinthekmt2amllgenecausingatypicalwiedemannsteinersyndromeintwounrelatedindividualsidentifiedbyclinicalexomesequencing AT lozanoreymundo denovovariantsinthekmt2amllgenecausingatypicalwiedemannsteinersyndromeintwounrelatedindividualsidentifiedbyclinicalexomesequencing AT leehane denovovariantsinthekmt2amllgenecausingatypicalwiedemannsteinersyndromeintwounrelatedindividualsidentifiedbyclinicalexomesequencing AT dorraninaghmeh denovovariantsinthekmt2amllgenecausingatypicalwiedemannsteinersyndromeintwounrelatedindividualsidentifiedbyclinicalexomesequencing AT mannjohn denovovariantsinthekmt2amllgenecausingatypicalwiedemannsteinersyndromeintwounrelatedindividualsidentifiedbyclinicalexomesequencing AT olaguepatriciaf denovovariantsinthekmt2amllgenecausingatypicalwiedemannsteinersyndromeintwounrelatedindividualsidentifiedbyclinicalexomesequencing AT mansnicole denovovariantsinthekmt2amllgenecausingatypicalwiedemannsteinersyndromeintwounrelatedindividualsidentifiedbyclinicalexomesequencing AT deignanjoshual denovovariantsinthekmt2amllgenecausingatypicalwiedemannsteinersyndromeintwounrelatedindividualsidentifiedbyclinicalexomesequencing AT vilaineric denovovariantsinthekmt2amllgenecausingatypicalwiedemannsteinersyndromeintwounrelatedindividualsidentifiedbyclinicalexomesequencing AT nelsonstanleyf denovovariantsinthekmt2amllgenecausingatypicalwiedemannsteinersyndromeintwounrelatedindividualsidentifiedbyclinicalexomesequencing AT grodywaynew denovovariantsinthekmt2amllgenecausingatypicalwiedemannsteinersyndromeintwounrelatedindividualsidentifiedbyclinicalexomesequencing AT quinteroriverafabiola denovovariantsinthekmt2amllgenecausingatypicalwiedemannsteinersyndromeintwounrelatedindividualsidentifiedbyclinicalexomesequencing |