Cargando…

Clinical and Neurobehavioral Features of Three Novel Kabuki Syndrome Patients with Mosaic KMT2D Mutations and a Review of Literature

Kabuki syndrome (KS) is a rare disorder characterized by multiple congenital anomalies and variable intellectual disability caused by mutations in KMT2D/MLL2 and KDM6A/UTX, two interacting chromatin modifier responsible respectively for 56–75% and 5–8% of the cases. To date, three KS patients with m...

Descripción completa

Detalles Bibliográficos
Autores principales: Lepri, Francesca Romana, Cocciadiferro, Dario, Augello, Bartolomeo, Alfieri, Paolo, Pes, Valentina, Vancini, Alessandra, Caciolo, Cristina, Squeo, Gabriella Maria, Malerba, Natascia, Adipietro, Iolanda, Novelli, Antonio, Sotgiu, Stefano, Gherardi, Renzo, Digilio, Maria Cristina, Dallapiccola, Bruno, Merla, Giuseppe
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5796032/
https://www.ncbi.nlm.nih.gov/pubmed/29283410
http://dx.doi.org/10.3390/ijms19010082
_version_ 1783297416992129024
author Lepri, Francesca Romana
Cocciadiferro, Dario
Augello, Bartolomeo
Alfieri, Paolo
Pes, Valentina
Vancini, Alessandra
Caciolo, Cristina
Squeo, Gabriella Maria
Malerba, Natascia
Adipietro, Iolanda
Novelli, Antonio
Sotgiu, Stefano
Gherardi, Renzo
Digilio, Maria Cristina
Dallapiccola, Bruno
Merla, Giuseppe
author_facet Lepri, Francesca Romana
Cocciadiferro, Dario
Augello, Bartolomeo
Alfieri, Paolo
Pes, Valentina
Vancini, Alessandra
Caciolo, Cristina
Squeo, Gabriella Maria
Malerba, Natascia
Adipietro, Iolanda
Novelli, Antonio
Sotgiu, Stefano
Gherardi, Renzo
Digilio, Maria Cristina
Dallapiccola, Bruno
Merla, Giuseppe
author_sort Lepri, Francesca Romana
collection PubMed
description Kabuki syndrome (KS) is a rare disorder characterized by multiple congenital anomalies and variable intellectual disability caused by mutations in KMT2D/MLL2 and KDM6A/UTX, two interacting chromatin modifier responsible respectively for 56–75% and 5–8% of the cases. To date, three KS patients with mosaic KMT2D deletions in blood lymphocytes have been described. We report on three additional subjects displaying KMT2D gene mosaics including one in which a single nucleotide change results in a new frameshift mutation (p.L1199HfsX7), and two with already-known nonsense mutations (p.R4484X and p.R5021X). Consistent with previously published cases, mosaic KMT2D mutations may result in mild KS facial dysmorphisms and clinical and neurobehavioral features, suggesting that these characteristics could represent the handles for genetic testing of individuals with slight KS-like traits.
format Online
Article
Text
id pubmed-5796032
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-57960322018-02-09 Clinical and Neurobehavioral Features of Three Novel Kabuki Syndrome Patients with Mosaic KMT2D Mutations and a Review of Literature Lepri, Francesca Romana Cocciadiferro, Dario Augello, Bartolomeo Alfieri, Paolo Pes, Valentina Vancini, Alessandra Caciolo, Cristina Squeo, Gabriella Maria Malerba, Natascia Adipietro, Iolanda Novelli, Antonio Sotgiu, Stefano Gherardi, Renzo Digilio, Maria Cristina Dallapiccola, Bruno Merla, Giuseppe Int J Mol Sci Case Report Kabuki syndrome (KS) is a rare disorder characterized by multiple congenital anomalies and variable intellectual disability caused by mutations in KMT2D/MLL2 and KDM6A/UTX, two interacting chromatin modifier responsible respectively for 56–75% and 5–8% of the cases. To date, three KS patients with mosaic KMT2D deletions in blood lymphocytes have been described. We report on three additional subjects displaying KMT2D gene mosaics including one in which a single nucleotide change results in a new frameshift mutation (p.L1199HfsX7), and two with already-known nonsense mutations (p.R4484X and p.R5021X). Consistent with previously published cases, mosaic KMT2D mutations may result in mild KS facial dysmorphisms and clinical and neurobehavioral features, suggesting that these characteristics could represent the handles for genetic testing of individuals with slight KS-like traits. MDPI 2017-12-28 /pmc/articles/PMC5796032/ /pubmed/29283410 http://dx.doi.org/10.3390/ijms19010082 Text en © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Case Report
Lepri, Francesca Romana
Cocciadiferro, Dario
Augello, Bartolomeo
Alfieri, Paolo
Pes, Valentina
Vancini, Alessandra
Caciolo, Cristina
Squeo, Gabriella Maria
Malerba, Natascia
Adipietro, Iolanda
Novelli, Antonio
Sotgiu, Stefano
Gherardi, Renzo
Digilio, Maria Cristina
Dallapiccola, Bruno
Merla, Giuseppe
Clinical and Neurobehavioral Features of Three Novel Kabuki Syndrome Patients with Mosaic KMT2D Mutations and a Review of Literature
title Clinical and Neurobehavioral Features of Three Novel Kabuki Syndrome Patients with Mosaic KMT2D Mutations and a Review of Literature
title_full Clinical and Neurobehavioral Features of Three Novel Kabuki Syndrome Patients with Mosaic KMT2D Mutations and a Review of Literature
title_fullStr Clinical and Neurobehavioral Features of Three Novel Kabuki Syndrome Patients with Mosaic KMT2D Mutations and a Review of Literature
title_full_unstemmed Clinical and Neurobehavioral Features of Three Novel Kabuki Syndrome Patients with Mosaic KMT2D Mutations and a Review of Literature
title_short Clinical and Neurobehavioral Features of Three Novel Kabuki Syndrome Patients with Mosaic KMT2D Mutations and a Review of Literature
title_sort clinical and neurobehavioral features of three novel kabuki syndrome patients with mosaic kmt2d mutations and a review of literature
topic Case Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5796032/
https://www.ncbi.nlm.nih.gov/pubmed/29283410
http://dx.doi.org/10.3390/ijms19010082
work_keys_str_mv AT leprifrancescaromana clinicalandneurobehavioralfeaturesofthreenovelkabukisyndromepatientswithmosaickmt2dmutationsandareviewofliterature
AT cocciadiferrodario clinicalandneurobehavioralfeaturesofthreenovelkabukisyndromepatientswithmosaickmt2dmutationsandareviewofliterature
AT augellobartolomeo clinicalandneurobehavioralfeaturesofthreenovelkabukisyndromepatientswithmosaickmt2dmutationsandareviewofliterature
AT alfieripaolo clinicalandneurobehavioralfeaturesofthreenovelkabukisyndromepatientswithmosaickmt2dmutationsandareviewofliterature
AT pesvalentina clinicalandneurobehavioralfeaturesofthreenovelkabukisyndromepatientswithmosaickmt2dmutationsandareviewofliterature
AT vancinialessandra clinicalandneurobehavioralfeaturesofthreenovelkabukisyndromepatientswithmosaickmt2dmutationsandareviewofliterature
AT caciolocristina clinicalandneurobehavioralfeaturesofthreenovelkabukisyndromepatientswithmosaickmt2dmutationsandareviewofliterature
AT squeogabriellamaria clinicalandneurobehavioralfeaturesofthreenovelkabukisyndromepatientswithmosaickmt2dmutationsandareviewofliterature
AT malerbanatascia clinicalandneurobehavioralfeaturesofthreenovelkabukisyndromepatientswithmosaickmt2dmutationsandareviewofliterature
AT adipietroiolanda clinicalandneurobehavioralfeaturesofthreenovelkabukisyndromepatientswithmosaickmt2dmutationsandareviewofliterature
AT novelliantonio clinicalandneurobehavioralfeaturesofthreenovelkabukisyndromepatientswithmosaickmt2dmutationsandareviewofliterature
AT sotgiustefano clinicalandneurobehavioralfeaturesofthreenovelkabukisyndromepatientswithmosaickmt2dmutationsandareviewofliterature
AT gherardirenzo clinicalandneurobehavioralfeaturesofthreenovelkabukisyndromepatientswithmosaickmt2dmutationsandareviewofliterature
AT digiliomariacristina clinicalandneurobehavioralfeaturesofthreenovelkabukisyndromepatientswithmosaickmt2dmutationsandareviewofliterature
AT dallapiccolabruno clinicalandneurobehavioralfeaturesofthreenovelkabukisyndromepatientswithmosaickmt2dmutationsandareviewofliterature
AT merlagiuseppe clinicalandneurobehavioralfeaturesofthreenovelkabukisyndromepatientswithmosaickmt2dmutationsandareviewofliterature