Broad neurodevelopmental features and cortical anomalies associated with a novel de novo KMT2A variant in Wiedemann-Steiner syndrome.

Filippo Brighina, Salvatore Mangano, Antonina Fontana, Giuseppe Donato Mangano, Cesare Gagliardo, Rosaria Nardello, Vincenzo Raieli, Paola Borgia, Vincenzo Salpietro, Federico Midiri

Risultato della ricerca: Articlepeer review


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.
Lingua originaleEnglish
Numero di pagine4
RivistaEuropean Journal of Medical Genetics
Stato di pubblicazionePublished - 2020

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)

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