ANCO-1; ANCO1; LZ16; T13
The ANKRD11 gene is associated with autosomal dominant KBG syndrome (MedGen UID: 66317) and Cornelia de Lange Syndrome (CdLS) (PMID: 25652421, 25125236).
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Invitae tests that include this gene:
The ANKRD11 gene encodes the ankyrin repeat domain 11 protein of largely unknown function. It has been shown to interact with histone deacetylases to repress transcription, and may also enhance the activity of the tumor suppressor p53.
ANKRD11 is associated with autosomal dominant KBG syndrome (MedGen UID: 66317). KBG syndrome is characterized by macrodontia of the central upper incisors, distinctive facial features (e.g., a triangular-shaped face, brachycephaly, hypertelorism, broad and bushy eyebrows, prominent nasal bridge, long philtrum, and thin upper lip), skeletal anomalies (e.g., delayed bone age, costovertebral anomalies, and large anterior fontanelle with delayed closure), short stature, seizures, and intellectual disability (PMID: 21782149). Speech delay, learning difficulties, and variable behavioral problems are also frequent (PMID: 27667800). Less common features include cutaneous toe syndactyly, a webbed/short neck, cryptorchidism, hearing loss, palatal defects (feeding difficulties), strabismus, and congenital heart defects (PMID: 17163996). As the dysmorphic features may be subtle, diagnosis may not occur until the permanent teeth are present (PMID: 27667800).
The ANKRD11 gene encodes the ankyrin repeat domain 11 protein of largely unknown function. It has been shown to interact with histone deacetylases to repress transcription and may also enhance the activity of the tumor suppressor p53 (PMID: 15184363, 18840648).
The ANKRD11 protein is found in a wide variety of tissues, including the brain, and is believed to be essential for neural development, likely explaining its association with cognitive impairments (PMID: 25556659). However, it is unclear how the loss of ANKRD11 function leads to the skeletal features of the condition (PMID: 27667800).
KBG syndrome is caused by pathogenic variants in, or deletion of, the ANKRD11 gene. Most ANKRD11 variants lead to loss of function of the ANKRD11 protein; however, no clear genotype-phenotype correlations have been established (PMID: 27667800).
KBG syndrome is inherited in an autosomal dominant manner. This means that an individual with a pathogenic variant has a 50% chance of passing the condition onto their offspring. Most cases of KBG syndrome occur spontaneously (i.e., an individual with a pathogenic variant has parents who do not have it); however, some are inherited from an affected parent. At-risk relatives can pursue testing for the specific familial variant.
Management guidelines for this condition have been proposed (PMID: 27667800). Investigations to consider for all newly-diagnosed patients include echocardiogram and the following assessments: palatal, hearing, vision, dental, developmental (cognitive/behavioral) as well as assessment for undescended testes in males.
Referrals and ongoing surveillance that may be required include:
Additionally, skeletal survey, bone age assessment, renal ultrasounds, and MRI brain scans may be indicated. Pharmaceuticals may include anti-seizure medications, medications for ADHD and anxiety, and growth hormone for short stature. Ototoxic drugs should be avoided because of the risk of hearing loss.
Review date: May 2018
Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).
Our sequence analysis covers clinically important regions of each gene, including coding exons and 10 to 20 base pairs of adjacent intronic sequence on either side of the coding exons in the transcript listed below. In addition, the analysis covers the select non-coding variants specifically defined in the table below. Any variants that fall outside these regions are not analyzed. Any limitations in the analysis of these genes will be listed on the report. Contact client services with any questions.
Based on validation study results, this assay achieves >99% analytical sensitivity and specificity for single nucleotide variants, insertions and deletions <15bp in length, and exon-level deletions and duplications. Invitae's methods also detect insertions and deletions larger than 15bp but smaller than a full exon but sensitivity for these may be marginally reduced. Invitae’s deletion/duplication analysis determines copy number at a single exon resolution at virtually all targeted exons. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. Certain types of variants, such as structural rearrangements (e.g. inversions, gene conversion events, translocations, etc.) or variants embedded in sequence with complex architecture (e.g. short tandem repeats or segmental duplications), may not be detected. Additionally, it may not be possible to fully resolve certain details about variants, such as mosaicism, phasing, or mapping ambiguity. Unless explicitly guaranteed, sequence changes in the promoter, non-coding exons, and other non-coding regions are not covered by this assay. Please consult the test definition on our website for details regarding regions or types of variants that are covered or excluded for this test. This report reflects the analysis of an extracted genomic DNA sample. In very rare cases, (circulating hematolymphoid neoplasm, bone marrow transplant, recent blood transfusion) the analyzed DNA may not represent the patient's constitutional genome.
|Gene||Transcript reference||Sequencing analysis||Deletion/Duplication analysis|