KDM6A Point Mutations Cause Kabuki Syndrome

  title={KDM6A Point Mutations Cause Kabuki Syndrome},
  author={Noriko Miyake and Seiji Mizuno and Nobuhiko Okamoto and Hirofumi Ohashi and Masaaki Shiina and Kazuhiro Ogata and Yoshinori Tsurusaki and Mitsuko Nakashima and Hirotomo Saitsu and Norio Niikawa and Naomichi Matsumoto},
  journal={Human Mutation},
Kabuki syndrome (KS) is a rare congenital anomaly syndrome characterized by a unique facial appearance, growth retardation, skeletal abnormalities, and intellectual disability. In 2010, MLL2 was identified as a causative gene. On the basis of published reports, 55–80% of KS cases can be explained by MLL2 abnormalities. Recently, de novo deletion of KDM6A has been reported in three KS patients, but point mutations of KDM6A have never been found. In this study, we investigated KDM6A in 32 KS… 

A three generation X‐linked family with Kabuki syndrome phenotype and a frameshift mutation in KDM6A

Two brothers with a mutation in KDM6A inherited from their mother and maternal grandmother are described, which represents the first instance of hereditary X‐linked Kabuki syndrome.

A novel de novo mutation involving the MLL2 gene in a Kabuki syndrome patient presenting with seizures.

The aim of the present report is to increase the awareness of Kabuki Syndrome among adult neurologists and to present a previously unreported non-sense mutation in the MLL2 gene.

Kabuki Syndrome

  • S. Jyonouchi
  • Medicine, Biology
    Encyclopedia of Medical Immunology
  • 2019
Most KS patients show increased susceptibility to infections and have reduced serum immunoglobulin levels, while some suffer also from autoimmune manifestations, such as idiopathic thrombocytopenic purpura, hemolytic anemia and other.

De novo exonic deletion of KDM6A in a Chinese girl with Kabuki syndrome: A case report and brief literature review

A de novo 227‐kb deletion in chromosome Xp11.3 of a 7‐year‐old Chinese girl with Kabuki syndrome is reported, which includes the upstream region and exons 1–2 of KDM6A and potentially causes haploinsuffiency of the gene.

MLL2 and KDM6A mutations in patients with Kabuki syndrome

High arched eyebrows, short fifth finger, and hypotonia in infancy were more frequent in the MLL2 mutation group than in the KDM6A mutation group, and short stature and postnatal growth retardation were observed in all individuals with KDM 6A mutations, but in only half of the group with M LL2 mutations.

Mutation Update for Kabuki Syndrome Genes KMT2D and KDM6A and Further Delineation of X‐Linked Kabuki Syndrome Subtype 2

A mutation screening in a case series of 347 unpublished patients identified 12 novel KDM6A mutations (KS type 2) and 208 mutations in KMT2D ( KS type 1), 132 of them novel.

Dissecting KMT2D missense mutations in Kabuki syndrome patients

The mutation spectrum of K MT2D and KDM6A in KS is expanded by identifying 37 new KMT2D sequence variants, and impaired H3K4 methyltransferase activity in 9 of the 14 mutant alleles is demonstrated, due in part to disruption of protein complex formation.

Kabuki syndrome: clinical and molecular characteristics

Because mutation detection rates rely on the accuracy of the clinical diagnosis and the inclusion or exclusion of atypical cases, recognition of KS will facilitate the identification of novel mutations.

Hypoglycemia in Kabuki syndrome

It is suggested that patients with KS may have hypoglycemia due to different mechanisms and that MLL2 gene may have a role in glucose physiology.

[Clinical diagnosis of Kabuki syndrome: phenotype and associated abnormalities in two new cases].

Two patients with clinical diagnosis of Kabuki syndrome are described, highlighting the phenotypic findings and associated malformations.



How genetically heterogeneous is Kabuki syndrome?: MLL2 testing in 116 patients, review and analyses of mutation and phenotypic spectrum

The largest yet reported cohort of 116 patients with Kabuki syndrome is presented, and the analyses of the phenotype indicates that MLL2 mutation-positive and -negative patients differ systematically, and genetic heterogeneity of KS is not as extensive as previously suggested.

Deletion of KDM6A, a histone demethylase interacting with MLL2, in three patients with Kabuki syndrome.

Kabuki make‐up and Turner syndromes in the same patient

A 2-year-old girl with clinical features of both Turner syndrome and Kabuki make-up syndrome is described, which has most of the features expected in a girl with 45,X, but in addition is microcephalic with the dysmorphic features of KabukiMake-up Syndrome.

A small and active ring x chromosome in a female with features of Kabuki syndrome

Methylation analyses of polymorphic alleles of the androgen receptor gene showed that both alleles were unmethylated suggesting an active ring chromosome, and a female patient with clinical features resembling Kabuki syndrome and a mos 45,X/46,X,r(X) karyotype is presented.

Kabuki make-up (Niikawa-Kuroki) syndrome: a study of 62 patients.

These 62 patients with the Kabuki make-up syndrome (KMS) were collected in a collaborative study among 33 institutions and analyzed clinically, cytogenetically, and epidemiologically to delineate the

Ring chromosome X in a child with manifestations of Kabuki syndrome.

Results of FISH and RT-PCR experiments indicate a large deletion of the X chromosome consistent with a small-ring X chromosome with approximate breakpoints near p11.2 and q13, comparable to the observation of others where an atypically severe phenotype has been associated with the presence of an r(X), or small mar(X).

Three patients with ring (X) chromosomes and a severe phenotype.

Three patients with mosaicism and a cell line containing a small ring (X) chromosome are described. Their phenotype is similar to several previously reported patients with a 45,X/46,X,r(X) karyotype

The UTX gene escapes X inactivation in mice and humans.

The characterization of a widely transcribed X- linked homologue of Uty, called Utx, is reported, which maps to the proximal region of the mouse X chromosome and which detects a human X-linked homologue at Xp11.2.