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

doi:10.3390/ijms19010082

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

Francesca Romana Lepri

¹,

^2,3,

⁴

⁵,

⁶,

⁴,

Gabriella Maria Squeo

²,

^2,3,

²,

¹,

⁵,

⁷,

Maria Cristina Digilio

⁸,

Bruno Dallapiccola

⁹ and

Giuseppe Merla

^2,*

Laboratory of Medical Genetics, Bambino Gesù Children’s Hospital, IRCCS, 00165 Rome, Italy

Division of Medical Genetics, IRCSS Casa Sollievo della Sofferenza Hospital, viale Cappuccini, 71013 San Giovanni Rotondo, Italy

PhD Program in Experimental and Regenerative Medicine, Faculty of Medicine, University of Foggia, 71122 Foggia, Italy

⁴

Department of Neurosciences, Child Neuropsychiatry Unit, Bambino Gesù Children’s Hospital, IRCCS, 00165 Rome, Italy

⁵

Child Neuropsychiatry Unit, Department of Clinical and Experimental Medicine, University of Sassari, 07100 Sassari, Italy

⁶

Neonatal Intensive Care Unit, Maggiore Hospital, 40133 Bologna, Italy

⁷

Child Neuropsychiatry Unit, UO Casalecchio Porretta Bologna District, 40124 Bologna, Italy

⁸

Medical Genetic Unit, Bambino Gesù Children’s, IRCCS, 00165 Rome, Italy

⁹

Scientific Directorate, Bambino Gesù Children’s Hospital, IRCCS, 00165 Rome, Italy

Author to whom correspondence should be addressed.

Int. J. Mol. Sci. 2018, 19(1), 82; https://doi.org/10.3390/ijms19010082

Received: 24 November 2017 / Revised: 21 December 2017 / Accepted: 23 December 2017 / Published: 28 December 2017

(This article belongs to the Special Issue Epigenetics of Neurodevelopmental Disorders)

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Abstract

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. View Full-Text

Keywords: kabuki syndrome; KMT2D/MLL2; mosaicism; developmental delay

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Lepri, F.R.; Cocciadiferro, D.; Augello, B.; Alfieri, P.; Pes, V.; Vancini, A.; Caciolo, C.; Squeo, G.M.; Malerba, N.; Adipietro, I.; Novelli, A.; Sotgiu, S.; Gherardi, R.; Digilio, M.C.; Dallapiccola, B.; Merla, G. Clinical and Neurobehavioral Features of Three Novel Kabuki Syndrome Patients with Mosaic KMT2D Mutations and a Review of Literature. Int. J. Mol. Sci. 2018, 19, 82. https://doi.org/10.3390/ijms19010082

AMA Style

Lepri FR, Cocciadiferro D, Augello B, Alfieri P, Pes V, Vancini A, Caciolo C, Squeo GM, Malerba N, Adipietro I, Novelli A, Sotgiu S, Gherardi R, Digilio MC, Dallapiccola B, Merla G. Clinical and Neurobehavioral Features of Three Novel Kabuki Syndrome Patients with Mosaic KMT2D Mutations and a Review of Literature. International Journal of Molecular Sciences. 2018; 19(1):82. https://doi.org/10.3390/ijms19010082

Chicago/Turabian Style

Lepri, Francesca Romana, Dario Cocciadiferro, Bartolomeo Augello, Paolo Alfieri, Valentina Pes, Alessandra Vancini, Cristina Caciolo, Gabriella Maria Squeo, Natascia Malerba, Iolanda Adipietro, Antonio Novelli, Stefano Sotgiu, Renzo Gherardi, Maria Cristina Digilio, Bruno Dallapiccola, and Giuseppe Merla. 2018. "Clinical and Neurobehavioral Features of Three Novel Kabuki Syndrome Patients with Mosaic KMT2D Mutations and a Review of Literature" International Journal of Molecular Sciences 19, no. 1: 82. https://doi.org/10.3390/ijms19010082

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

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