A Novel Intronic KMT2D Variant as a Cause of Kabuki Syndrome: A Case Report

Abstract

Kabuki syndrome (KS) is an autosomal dominant genetic disorder in which most cases are caused by de novo mutations. KS type 1 is caused by mutations in KMT2D (OMIM: #147920) and is more common. KS type 2 is caused by mutations in KDM6A (OMIM: #300867). Both genes encode proteins that modify histones and are involved in epigenetic regulation. The enzyme histone-lysine N-methyltransferase 2D, the product of KMT2D, is expressed in most adult tissues and is essential for early embryonic development. The main clinical manifestations of KS include dysmorphic facial features, such as elongated palpebral fissures, eversion of the lateral third of the lower eyelids, and short nasal columella with a broad and depressed nasal tip. Additionally, patients also present with skeletal abnormalities, dermatoglyphic features, mild-to-moderate intellectual disability, hearing loss, and postnatal growth deficiency. We describe an 11-year-old girl from Colombia, who presented with characteristic clinical signs of KS. Genetic studies showed a KMT2D intronic variant (KMT2D NM_003482.3: c.511-2A> T) as a cause of KS.

Single-Cell Transcriptome Analysis Defines Expression of Kabuki Syndrome-Associated KMT2D Targets and Interacting Partners

“…Kabuki syndrome (KS) is a rare genetic disorder caused by mutations in the histone modifier genes encoding histone H3 lysine 4 methyltransferase (KMT2D) and histone H3 lysine 27 demethylase (KDM6A) (OMIM: #147920 and #300867) [1,2]. The main clinical manifestations of KS include dysmorphic facial features, skeletal abnormalities, intellectual disability, hearing loss, and retarded postnatal growth.…”

Case report: A study on the de novo KMT2D variant of Kabuki syndrome with Goodpasture’s syndrome by whole exome sequencing

“…Kabuki syndrome (KS; OMIM #147920) is a rare, multiple malformation syndrome characterized by distinctive facial features combined with skeletal abnormalities, immunological defects, and intellectual disability (1,2,3). The prevalence of KS is around 1 in 32,000 live births (1).…”