Micro-Del/Micro-Dup Reference Standard

What are microdeletions and microduplications?

Microdeletions and microduplications refer to the deletion or duplication of small fragments on chromosomes. These fragments are usually between 1kb and several megabases in size.

What are microdeletion/microduplication reference standards?

A microdeletion/microduplication reference standard is a quality control tool. It is a known, precisely designed, and validated DNA sample containing a specific, well-defined microdeletion or microduplication.

Its primary functions and importance lie in:

1.Quality Control (QC): When performing genetic testing (such as MLPA, CMA, and NGS) in the laboratory, reference standards are required to verify the accuracy and reliability of the entire experimental process, from DNA extraction and amplification to detection. If the reference standard produces the expected results, it indicates that the experimental process is flawless, and the results from the patient sample are reliable.

2.Result Verification and Validation: When a suspected microdeletion/microduplication is found in a patient sample, the corresponding reference standard can be used for simultaneous testing and confirmation. This is like using a "standard ruler" to measure the length of an object to ensure accurate measurements.

Instrument Calibration and Performance Validation: When new equipment is put into use or a new testing method is established, reference standards must be used to calibrate and validate the sensitivity and specificity of the instrument and method.

What diseases are microdeletion and microduplication standards related to?

Microdeletion/microduplication syndromes are a significant cause of numerous diseases, particularly closely associated with the following:

Congenital developmental abnormalities:Intellectual disability and developmental delay、Autism spectrum disorder (ASD)

、Congenital heart disease、Facial deformities such as cleft lip and palate

Specific classic syndromes：

22q11.2 deletion syndrome (DiGeorge syndrome): The most common syndrome, characterized by heart defects, cleft palate, immunosuppression, hypocalcemia, and learning difficulties.

Williams syndrome (7q11.23 deletion): Characterized by an "elfin" appearance, cardiovascular disease, a sociable personality, intellectual disability, and exceptional musical talent.

Prader-Willi syndrome (15q11-q13 deletion): Hypotonia and feeding difficulties in infancy, followed by obesity, intellectual disability, and behavioral problems in childhood.

Angelman syndrome (maternal deletion of 15q11-q13): Characterized by severe intellectual disability, language impairment, ataxia, and frequent laughter/excitement. 

1p36 deletion syndrome: Manifestations include intellectual disability, growth retardation, epilepsy, and distinctive facial features.

Cri du chat syndrome (5p deletion): Infants experience a cat-like cry, accompanied by severe intellectual disability and microcephaly.

Oncological diseases: Many cancers are associated with the deletion or amplification of specific genes, which are also considered copy number variations. For example, HER2 gene amplification is associated with targeted therapies for certain breast cancers.

What are the application scenarios?

Microdeletion/microduplication detection technology is primarily used in the following clinical and research scenarios:

1. Prenatal diagnosis:

Non-invasive DNA prenatal testing (NIPT Plus): By drawing maternal peripheral blood, the fetus can be screened for common chromosomal aneuploidies (such as Down syndrome) and some common microdeletion syndromes.

2. Confirmatory diagnosis for high-risk pregnancies: If NIPT, ultrasound (with structural abnormalities), or serological screening indicates high risk, fetal cells are obtained through amniocentesis or chorionic villus sampling for chromosomal microarray analysis (CMA) to confirm the presence of microdeletions/microduplications.

3. Diagnosis of genetic diseases in children and adults:

For children with unexplained intellectual disability, developmental delay, autism, or multiple congenital malformations, CMA is typically the preferred genetic test, detecting the cause in approximately 15-20% of cases.

4. Infertility and Miscarriage Cause Investigation:

Testing couples experiencing recurrent miscarriage or embryos to identify chromosomal abnormalities (including microdeletions/microduplications) that may have led to developmental arrest.

5. Cancer Genomics:

Examining DNA from tumor tissue in cancer patients to identify gene copy number changes associated with cancer development, progression, and targeted therapy. This is used for classification, prognosis, and medication guidance (e.g., HER2 testing).

6. Scientific Research:

Used to discover new disease-associated gene loci and study the relationship between gene function and dose-response.