Topics

Identification of KMT2D and KDM6A variants by targeted sequencing from patients with Kabuki syndrome and other congenital disorders.

07:00 EST 11th January 2020 | BioPortfolio

Summary of "Identification of KMT2D and KDM6A variants by targeted sequencing from patients with Kabuki syndrome and other congenital disorders."

Kabuki syndrome (KS) is a rare congenital disorder characterized by distinctive facies, postnatal growth deficiency, cardiac defects and skeletal anomalies. Studies have determined that pathogenic variants of the lysine-specific methyltransferase 2D (KMT2D) and lysine-specific demethylase 6A (KDM6A) genes are the major causes of KS. The two genes encode different histone-modifying enzymes that are found in the same protein complex that is critical for cell differentiation during development. Here we report the results from next-generation sequencing of genomic DNA from 13 patients who had a clinical diagnosis of KS based on facial dysmorphism and other KS-specific cardinal phenotypes. Nine of the 13 patients were confirmed to be carrying heterozygous pathogenic KMT2D variants, seven of which were truncating and two were missense substitutions. Overall, we uncovered 11 novel variants - nine in KMT2D and two in KDM6A. Seven of the novel variants (all KMT2D) were likely causative of the KS phenotype. Our study expands the number of naturally occurring KMT2D and KDM6A variants. The discovery of novel pathogenic variants will add to the knowledge on disease-causing variants and the relevance of missense variants in KS.

Affiliation

Journal Details

This article was published in the following journal.

Name: Gene
ISSN: 1879-0038
Pages: 144360

Links

DeepDyve research library

PubMed Articles [34580 Associated PubMed Articles listed on BioPortfolio]

The phenotypic spectrum of Kabuki syndrome in patients of Chinese descent: A case series.

Kabuki syndrome (KS) is a rare disorder of transcriptional regulation with a complex phenotype that includes cranio-facial dysmorphism, intellectual disability, hypotonia, failure to thrive, short sta...

Holoprosencephaly in Kabuki syndrome.

Kabuki syndrome is a rare, multi-systemic disorder of chromatin regulation due to mutations in either KMT2D or KDM6A that encode a H3K4 methyltransferase and an H3K27 demethylase, respectively. The as...

Whole exome and targeted gene sequencing to detect pathogenic recessive variants in early onset cerebellar ataxia.

Over 100 genetically distinct causal known loci for hereditary ataxia phenotype poses a challenge for diagnostic work-up for ataxia patients in a clinically relevant time and precision. In the present...

High-throughput Sequencing of Subcutaneous Panniculitis-like T-Cell Lymphoma Reveals Candidate Pathogenic Mutations.

Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a malignant primary cutaneous T-cell lymphoma that is challenging to distinguish from other neoplastic and reactive panniculitides. In an atte...

Loss of KDM6A confers drug resistance in acute myeloid leukemia.

Acute myeloid leukemia (AML) is an aggressive hematologic neoplasm resulting from the malignant transformation of myeloid progenitors. Despite intensive chemotherapy leading to initial treatment respo...

Clinical Trials [3948 Associated Clinical Trials listed on BioPortfolio]

Improving Genetic Counseling for Patients With Spina Bifida Using Next Generation Sequencing

The main objective is to improve genetic counseling in patients with Spina Bifida, by the characterization of variants in new genes using high throughput sequencing either on a panel of ta...

Various Type of Genetic Events in Patients With Intellectual Disability

Currently, for a patient with intellectual disability without a recognizable syndrome (most cases), the way to diagnosis is often long, tedious and expensive because different approaches a...

Exome Sequencing Study in Cardiomyopathy to Identify New Risk Variants

Genetic mutations has been proved to be associated wth the onset of cardiomyopathy. In the present study, we intend to identify new related variants or genes. From March, 2003 to November,...

Evaluation of the Efficacy of the Sequencing Method by Gene-panel

In order to accelerate the identification of genes responsibles of PID, and to improve the diagnosis of PID, we would like to validate a rapid and targeted method of high-throughput sequen...

Targeted Next-generation Sequencing Panel for Identification of Germline Mutations in Early Onset Cancers With Sporadic or Hereditary Presentation

Despite relevant clinical and/or familial presentations suggesting a hereditary predisposition (early-onset, multiple primary tumors, familial aggregation), targeted genomic analysis based...

Medical and Biotech [MESH] Definitions

Direct nucleotide sequencing of gene fragments from multiple housekeeping genes for the purpose of phylogenetic analysis, organism identification, and typing of species, strain, serovar, or other distinguishable phylogenetic level.

Radiotherapy where cytotoxic radionuclides are linked to antibodies in order to deliver toxins directly to tumor targets. Therapy with targeted radiation rather than antibody-targeted toxins (IMMUNOTOXINS) has the advantage that adjacent tumor cells, which lack the appropriate antigenic determinants, can be destroyed by radiation cross-fire. Radioimmunotherapy is sometimes called targeted radiotherapy, but this latter term can also refer to radionuclides linked to non-immune molecules (see RADIOTHERAPY).

Techniques of nucleotide sequence analysis that increase the range, complexity, sensitivity, and accuracy of results by greatly increasing the scale of operations and thus the number of nucleotides, and the number of copies of each nucleotide sequenced. The sequencing may be done by analysis of the synthesis or ligation products, hybridization to preexisting sequences, etc.

The identification, analysis, and resolution of moral problems that arise in the care of patients. (Bioethics Thesaurus)

A form of male HYPOGONADISM, characterized by the presence of an extra X CHROMOSOME, small TESTES, seminiferous tubule dysgenesis, elevated levels of GONADOTROPINS, low serum TESTOSTERONE, underdeveloped secondary sex characteristics, and male infertility (INFERTILITY, MALE). Patients tend to have long legs and a slim, tall stature. GYNECOMASTIA is present in many of the patients. The classic form has the karyotype 47,XXY. Several karyotype variants include 48,XXYY; 48,XXXY; 49,XXXXY, and mosaic patterns ( 46,XY/47,XXY; 47,XXY/48,XXXY, etc.).

Quick Search


DeepDyve research library

Relevant Topics

DNA sequencing
DNA sequencing is the process of determining the precise order of nucleotides within a DNA molecule. During DNA sequencing, the bases of a small fragment of DNA are sequentially identified from signals emitted as each fragment is re-synthesized from a ...

Congenital Diseases
Congenital conditions are those which are present from birth. They include structural deformities or loss of function in organs such as the <!--LGfEGNT2Lhm-->heart, gut or skeletal system. They can be corrected by <!--LGfEGNT2Lhm-->surgery, m...


Searches Linking to this Article