Tags

Type your tag names separated by a space and hit enter

Genomic findings in patients with clinical suspicion of 22q11.2 deletion syndrome.
J Appl Genet 2017; 58(1):93-98JA

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.

Authors+Show Affiliations

Department of Biology and Genetics, Medical University of Gdansk, 1 Debinki Street, 80-211, Gdansk, Poland.General Nursery, Medical University of Gdansk, 7 Debinki Street, 80-211, Gdansk, Poland.Department of Social Pediatrics, Wroclaw Medical University, 5 Bartla Street, 51-618, Wroclaw, Poland.Department of Genetics, Wroclaw Medical University, 1 Marcinkowskiego Street, 50-368, Wroclaw, Poland.Department of Social Pediatrics, Wroclaw Medical University, 5 Bartla Street, 51-618, Wroclaw, Poland.Department of Genetics, Wroclaw Medical University, 1 Marcinkowskiego Street, 50-368, Wroclaw, Poland.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.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.

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 -