1. Broad neurodevelopmental features and cortical anomalies associated with a novel de novo KMT2A variant in Wiedemann-Steiner syndrome
- Author
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Vincenzo Salpietro, Federico Midiri, Giuseppe Donato Mangano, Vincenzo Raieli, Salvatore Mangano, Filippo Brighina, Rosaria Nardello, Paola Borgia, Cesare Gagliardo, Antonina Fontana, and Nardello R, Mangano GD, Fontana A, Gagliardo C, Midiri F, Borgia P, Brighina F, Raieli V, Mangano S, Salpietro V.
- Subjects
0301 basic medicine ,Male ,Developmental Disabilities ,030105 genetics & heredity ,Biology ,Focal cortical dysplasia ,Palilalia ,Frameshift mutation ,03 medical and health sciences ,Hypertrichosis cubiti ,Intellectual Disability ,Genetics ,medicine ,Humans ,Child ,Frameshift Mutation ,Genetics (clinical) ,Cerebral Cortex ,Wiedemann-steiner syndrome ,Genetic disorder ,General Medicine ,Histone-Lysine N-Methyltransferase ,Syndrome ,KMT2A ,Cortical dysplasia ,medicine.disease ,Malformations of Cortical Development ,030104 developmental biology ,Wiedemann-Steiner syndrome ,Autism spectrum disorder ,biology.protein ,medicine.symptom ,Myeloid-Lymphoid Leukemia Protein - Abstract
Wiedemann-Steiner syndrome (WDSTS) is a rare genetic disorder including developmental delay/intellectual disability (DD/ID), hypertrichosis cubiti, short stature, and distinctive facial features, caused by mutation in KMT2A gene, which encodes a histone methyltransferase (H3K4) that regulates chromatin-mediated transcription. Different neurodevelopmental phenotypes have been described within the WDSTS spectrum, including a peculiar Autism Spectrum Disorder (ASDs) subtype in some affected individuals. Here, we report a 9-year-old Caucasian male found by next-generation panel sequencing to carry a novel heterozygous de novo KMT2A frameshift variant (NM_001197104.2:c.4433delG; p. Arg1478LeufsTer108). This boy presented a WDSTS phenotype associated with broad neurodevelopmental features, including an unusual speech difficulty (i.e., palilalia), and brain imaging studies revealed an array of cortical anomalies (e.g., frontal simplified gyration, focal frontal cortical dysplasia). These clinical and radiological observations expand the known WDSTS-related neurodevelopmental phenotypes and further strengthen the important role of KMT2A in brain function and cortical development.
- Published
- 2020