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    MLPA Dummy Report

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    Aakash verma
    1) Homozygous deletion of exon 7 and exon 8 was detected in the patient's SMN1 gene, consistent with a diagnosis of Spinal Muscular Atrophy (SMA). No deletions or duplications were found in the SMN2 gene. 2) Genetic counseling is recommended based on the results. 3) Multiplex Ligation-dependent Probe Amplification (MLPA) was used to analyze copy number changes in exons 7 and 8 of the SMN1 and SMN2 genes.

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    MLPA Dummy Report

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    Aakash verma
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    1) Homozygous deletion of exon 7 and exon 8 was detected in the patient's SMN1 gene, consistent with a diagnosis of Spinal Muscular Atrophy (SMA). No deletions or duplications were found in the SMN2 gene. 2) Genetic counseling is recommended based on the results. 3) Multiplex Ligation-dependent Probe Amplification (MLPA) was used to analyze copy number changes in exons 7 and 8 of the SMN1 and SMN2 genes.

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    1) Homozygous deletion of exon 7 and exon 8 was detected in the patient's SMN1 gene, consistent with a diagnosis of Spinal Muscular Atrophy (SMA). No deletions or duplications were found in the SMN2 gene. 2) Genetic counseling is recommended based on the results. 3) Multiplex Ligation-dependent Probe Amplification (MLPA) was used to analyze copy number changes in exons 7 and 8 of the SMN1 and SMN2 genes.

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    © All Rights Reserved
    Download as PDF, TXT or read online from Scribd
    Download as pdf or txt
    70 views3 pages

    MLPA Dummy Report

    Uploaded by

    Aakash verma
    1) Homozygous deletion of exon 7 and exon 8 was detected in the patient's SMN1 gene, consistent with a diagnosis of Spinal Muscular Atrophy (SMA). No deletions or duplications were found in the SMN2 gene. 2) Genetic counseling is recommended based on the results. 3) Multiplex Ligation-dependent Probe Amplification (MLPA) was used to analyze copy number changes in exons 7 and 8 of the SMN1 and SMN2 genes.

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    of 3

    Department of Molecular Genetics & Genomics

    Patient information Ref. Doctor/ Hospital/ Specimen


    Patient Name: Ref Doctor:
    Barcode: Ref Hospital:
    Visit ID: Sample type: EDTA blood
    Age/Gender: Received date:
    Test name: SMA analysis by MLPA Reported date:

    SPINAL MUSCULAR ATROPHY (SMA) DELETION AND DUPLICATION ANALYSIS

    Referral Reason: ---------reported with absence of deep tendon reflexes in all limbs, the sample was
    referred for MLPA of SMN-1 gene

    • HOMOZYGOUS DELETION OF EXON 7 AND EXON 8 DETECTED IN SMN1 GENE.


    Test Result:
    • NO DELETION OR DUPLICATION DETECTED IN SMN2 GENE.

    Interpretation: The presence of homozygous deletion of exon7 and exon8 in SMN1 gene is consistent
    with the diagnosis of Spinal Muscular Atrophy in this individual. There are no deletion or duplications
    detected in SMN2 gene.

    6-3-862/A, Lal Bungalow, Ameerpet, Hyderabad – 500016, [email protected],


    Ph: +91 9542129919
    Recommendations:
    • Genetic Counselling and clinical correlation is recommended

    Methodology:
    Multiplex Ligation-dependent probe amplification (MLPA) method is used for the detection of copy
    number changes of Exons 7 and 8 of SMN1 and SMN2. Coffalyser software is used for data analysis.
    DNA was isolated from the provided sample using commercial kit according to manufacturer’s
    instructions and was subjected for MLPA analysis.

    Clinical Sensitivity - MLPA

    SMN1 deletions will be detected in over 99% of individuals with Spinal Muscular Atrophy in either the
    homozygous state (95% to 98% of affected individuals) or in the compound heterozygous state with
    another pathogenic variant (2% to 5% of affected individuals) (Rudnik- Schoneborn et al. 2012. PubMed ID:
    22510849).

    Introduction
    Spinal muscular atrophy (SMA) is an autosomal recessive neurodegenerative disorder with variable age at
    onset and severity, characterized by progressive degeneration of the lower motor neurons in the spinal
    cord and brain stem, leading to muscle weakness, and in its most common form, respiratory failure by age
    two. Complications of SMA may include poor weight gain, sleep difficulties, pneumonia, scoliosis, and joint
    deformities. In severely affected individuals, abnormal fetal ultrasound findings may include congenital
    joint contractures, polyhydramnios, and decreased fetal movement.3 Treatment is supportive. Targeted
    therapies may be available for some individuals. Approximately 94% of affected individuals have 0 copies of
    the SMN1 gene; in these individuals an increase in the number of copies of the SMN2 gene correlate s with
    reduced disease severity.4

    Genetics:
    Two nearly identical genes SMN1 and SMN2 located on complex region of chromosome 5 at band q13.2
    plays crucial role in SMA. Most individuals have two copies of each gene. SMN1 gene codes the survival of
    motor neuron protein (SMN) and plays a crucial role in survival of motor neurons. SMN2, is a complicated
    inverted repeat area displaying high instability, leading to frequent deletions and gene conversions. SMN1
    and SMN2 can only be distinguished by two single nucleotide differences: one in exon 7 and one in exon 8.
    The single nucleotide difference in exon 7 of SMN2 affects mRNA splicing resulting in an altered SMN
    protein with a limited half-life and function. The majority 95-98% of SMA patients show homozygous
    deletion of exon 7 in SMN1 gene which encodes the full-length survival motor neuron protein (Prior and
    Finanger. 2016. PubMed ID: 20301526) and SMA carriers can be identified by the presence of only one
    single SMN1 exon 7 copy. Determining the SMN2 copy number is important in SMA patients because more
    the copy number of SMN2 gene, less severe is the disease

    6-3-862/A, Lal Bungalow, Ameerpet, Hyderabad – 500016, [email protected],


    Ph: +91 9542129919
    Limitations of the test:

    This test cannot detect copy number neutral inversions, translocations, and methylation changes. All possible
    causes of the syndromes included cannot be detected as the probe mix has limited number of probes for each
    chromosomal region. The detection rate may vary between syndromes, depending on the heterogeneity of the
    disorder. Even when MLPA does not detect any aberrations, the possibility remains that biological changes in
    that gene or chromosomal region do exist but remain undetected. Sequence changes (e.g.SNPs, point mutations,
    small indels) in the target sequence or even when >20nt from the probe ligation site detected by a probe can
    affect the results. Sensitivity & specificity of the assay may be influenced by the quality of the specimen. The
    given test result should be interpreted in context of all available clinical findings. This method cannot detect point
    mutation in the SMN1/SMN2 gene. Some individuals have two copies of SMN1 on just one chromosome and no
    copies of SMN1 on the second chromosome, this individual will be a carrier but this will not be detected by this test.

    * It is presumed that the specimen used to perform the test belongs to the patient specified above, such verification
    having been carried out at the collection level of the sample. This test does not report any other mutations other than
    SMN as it is a targeted test.

    Although all precautions are taken while conducting these tests, there is a standard error rate of approximate 1% in all
    genetic tests and this should be taken into consideration before any clinical decision.

    False-positive or false-negative results may occur for reasons that include genetic variants, technical handling, blood
    transfusions, bone marrow transplantation, mislabelling of samples, or erroneous representation of family
    relationships.

    References:

    1. Katharina J Hoff (2009): The effect of sequencing errors on metagenomic gene prediction. BMC Genomics, 10:520.
    2. Alias L et al. (2014). Improving detection and genetic counselling in carriers of spinal muscular atrophy with
    two copies of the SMN1 gene. Clin Genet. 85:470-475
    3. Ben-Sachar S et al. (2011). Large-scale population screening for spinal muscular atrophy: clinical
    implications. Genet Med. 13:110-114
    4. Feldkötter M, Schwarzer V, Wirth R, Wienker TF, Wirth B. Quantitative analyses of SMN1 and SMN2 based on real-
    time light Cycler PCR: fast and highly reliable carrier testing and prediction of severity of spinal muscular atrophy. Am J
    Hum Genet. 2002 Feb;70(2):358-368.
    --- End of Report ---

    A. Radhika Dr. Naushad SM Dr. Kiran Kumar

    Co-Head Genomics Chief Scientific Officer Consultant Genomics

    6-3-862/A, Lal Bungalow, Ameerpet, Hyderabad – 500016, [email protected],


    Ph: +91 9542129919

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