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Genomic findings in patients with clinical suspicion of 22q11.2 deletion syndrome.

Abstract

Chromosome 22q11.2 deletion syndrome, one of the most common human genomic syndromes, has highly heterogeneous clinical presentation. Patients usually harbor a 1.5 to 3 Mb hemizygous deletion at chromosome 22q11.2, resulting in pathognomic TBX1, CRKL and/or MAPK1 haploinsufficiency. However, there are some individuals with clinical features resembling the syndrome who are eventually diagnosed with genomic disorders affecting other chromosomal regions. The objective of this study was to evaluate the additive value of high-resolution array-CGH testing in the cohort of 41 patients with clinical features of 22q11.2 deletion syndrome and negative results of standard cytogenetic diagnostic testing (karyotype and FISH for 22q11.2 locus). Array-CGH analysis revealed no aberrations at chromosomes 22 or 10 allegedly related to the syndrome. Five (12.2 %) patients were found to have other genomic imbalances, namely 17q21.31 microdeletion syndrome (MIM#610443), 1p36 deletion syndrome (MIM#607872), NF1 microduplication syndrome (MIM#613675), chromosome 6pter-p24 deletion syndrome (MIM#612582) and a novel interstitial deletion at 3q26.31 of 0.65 Mb encompassing a dosage-dependent gene NAALADL2. Our study demonstrates that the implementation of array-CGH into the panel of classic diagnostic procedures adds significantly to their efficacy. It allows for detection of constitutional genomic imbalances in 12 % of subjects with negative result of karyotype and FISH targeted for 22q11.2 region. Moreover, if used as first-tier genetic test, the method would provide immediate diagnosis in ∼40 % phenotypic 22q11.2 deletion subjects.

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  • Authors+Show Affiliations

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    Department of Biology and Genetics, Medical University of Gdansk, 1 Debinki Street, 80-211, Gdansk, Poland.

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    General Nursery, Medical University of Gdansk, 7 Debinki Street, 80-211, Gdansk, Poland.

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    Department of Social Pediatrics, Wroclaw Medical University, 5 Bartla Street, 51-618, Wroclaw, Poland.

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    Department of Genetics, Wroclaw Medical University, 1 Marcinkowskiego Street, 50-368, Wroclaw, Poland.

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    Department of Social Pediatrics, Wroclaw Medical University, 5 Bartla Street, 51-618, Wroclaw, Poland.

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    Department of Genetics, Wroclaw Medical University, 1 Marcinkowskiego Street, 50-368, Wroclaw, Poland.

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    Department of Biology and Genetics, Medical University of Gdansk, 1 Debinki Street, 80-211, Gdansk, Poland.

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    Department of Biology and Genetics, Medical University of Gdansk, 1 Debinki Street, 80-211, Gdansk, Poland.

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    Department of Biology and Genetics, Medical University of Gdansk, 1 Debinki Street, 80-211, Gdansk, Poland.

    Department of Biology and Genetics, Medical University of Gdansk, 1 Debinki Street, 80-211, Gdansk, Poland. b.lipska@gumed.edu.pl.

    Source

    Journal of applied genetics 58:1 2017 Feb pg 93-98

    MeSH

    Abnormalities, Multiple
    Chromosome Deletion
    Chromosome Disorders
    Chromosome Duplication
    Chromosomes, Human, Pair 1
    Chromosomes, Human, Pair 17
    Chromosomes, Human, Pair 6
    Comparative Genomic Hybridization
    DiGeorge Syndrome
    Eye Abnormalities
    Facies
    Female
    Hearing Loss
    Heart Defects, Congenital
    Humans
    Hypertelorism
    In Situ Hybridization, Fluorescence
    Intellectual Disability
    Karyotyping
    Male
    Neurofibromatoses

    Pub Type(s)

    Journal Article

    Language

    eng

    PubMed ID

    27629806

    Citation

    Koczkowska, Magdalena, et al. "Genomic Findings in Patients With Clinical Suspicion of 22q11.2 Deletion Syndrome." Journal of Applied Genetics, vol. 58, no. 1, 2017, pp. 93-98.
    Koczkowska M, Wierzba J, Śmigiel R, et al. Genomic findings in patients with clinical suspicion of 22q11.2 deletion syndrome. J Appl Genet. 2017;58(1):93-98.
    Koczkowska, M., Wierzba, J., Śmigiel, R., Sąsiadek, M., Cabała, M., Ślężak, R., ... Lipska-Ziętkiewicz, B. S. (2017). Genomic findings in patients with clinical suspicion of 22q11.2 deletion syndrome. Journal of Applied Genetics, 58(1), pp. 93-98. doi:10.1007/s13353-016-0366-1.
    Koczkowska M, et al. Genomic Findings in Patients With Clinical Suspicion of 22q11.2 Deletion Syndrome. J Appl Genet. 2017;58(1):93-98. PubMed PMID: 27629806.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Genomic findings in patients with clinical suspicion of 22q11.2 deletion syndrome. AU - Koczkowska,Magdalena, AU - Wierzba,Jolanta, AU - Śmigiel,Robert, AU - Sąsiadek,Maria, AU - Cabała,Magdalena, AU - Ślężak,Ryszard, AU - Iliszko,Mariola, AU - Kardaś,Iwona, AU - Limon,Janusz, AU - Lipska-Ziętkiewicz,Beata S, Y1 - 2016/09/14/ PY - 2016/04/25/received PY - 2016/08/29/accepted PY - 2016/08/15/revised PY - 2016/9/16/pubmed PY - 2017/2/7/medline PY - 2016/9/16/entrez KW - 17q21.31 microdeletion syndrome KW - 22q11.2 deletion syndrome KW - Array comparative genomic hybridization KW - NAALADL2 KW - NF1 microduplication syndrome KW - chromosome 6p25.3p25.2 deletion SP - 93 EP - 98 JF - Journal of applied genetics JO - J. Appl. Genet. VL - 58 IS - 1 N2 - Chromosome 22q11.2 deletion syndrome, one of the most common human genomic syndromes, has highly heterogeneous clinical presentation. Patients usually harbor a 1.5 to 3 Mb hemizygous deletion at chromosome 22q11.2, resulting in pathognomic TBX1, CRKL and/or MAPK1 haploinsufficiency. However, there are some individuals with clinical features resembling the syndrome who are eventually diagnosed with genomic disorders affecting other chromosomal regions. The objective of this study was to evaluate the additive value of high-resolution array-CGH testing in the cohort of 41 patients with clinical features of 22q11.2 deletion syndrome and negative results of standard cytogenetic diagnostic testing (karyotype and FISH for 22q11.2 locus). Array-CGH analysis revealed no aberrations at chromosomes 22 or 10 allegedly related to the syndrome. Five (12.2 %) patients were found to have other genomic imbalances, namely 17q21.31 microdeletion syndrome (MIM#610443), 1p36 deletion syndrome (MIM#607872), NF1 microduplication syndrome (MIM#613675), chromosome 6pter-p24 deletion syndrome (MIM#612582) and a novel interstitial deletion at 3q26.31 of 0.65 Mb encompassing a dosage-dependent gene NAALADL2. Our study demonstrates that the implementation of array-CGH into the panel of classic diagnostic procedures adds significantly to their efficacy. It allows for detection of constitutional genomic imbalances in 12 % of subjects with negative result of karyotype and FISH targeted for 22q11.2 region. Moreover, if used as first-tier genetic test, the method would provide immediate diagnosis in ∼40 % phenotypic 22q11.2 deletion subjects. SN - 2190-3883 UR - https://www.unboundmedicine.com/medline/citation/27629806/Genomic_findings_in_patients_with_clinical_suspicion_of_22q11_2_deletion_syndrome_ L2 - https://dx.doi.org/10.1007/s13353-016-0366-1 DB - PRIME DP - Unbound Medicine ER -