Τίτλος:
Application of high-resolution array comparative genomic hybridization in children with unknown syndromic microcephaly
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
BackroundMicrocephaly can either be isolated or it may coexist with other neurological entities and/or multiple congenital anomalies, known as syndromic microcephaly. Although many syndromic cases can be classified based on the characteristic phenotype, some others remain uncertain and require further investigation. The present study describes the application of array-comparative genomic hybridization (array-CGH) as a diagnostic tool for the study of patients with clinically unknown syndromic microcephaly.MethodsFrom a cohort of 210 unrelated patients referred with syndromic microcephaly, we applied array-CGH analysis in 53 undiagnosed cases. In all the 53 cases except one, previous standard karyotype was negative. High-resolution 4 × 180K and 1 × 244K Agilent arrays were used in this study.ResultsIn 25 out of the 53 patients with microcephaly among other phenotypic anomalies, array-CGH revealed copy number variations (CNVs) ranging in size between 15 kb and 31.6 Mb. The identified CNVs were definitely causal for microcephaly in 11/53, probably causal in 7/53, and not causal for microcephaly in 7/53 patients. Genes potentially contributing to brain deficit were revealed in 16/53 patients.ConclusionsArray-CGH contributes to the elucidation of undefined syndromic microcephalic cases by permitting the discovery of novel microdeletions and/or microduplications. It also allows a more precise genotype-phenotype correlation by the accurate definition of the breakpoints in the deleted/duplicated regions. © 2017 International Pediatric Research Foundation, Inc.
Συγγραφείς:
Tsoutsou, E.
Tzetis, M.
Giannikou, K.
Braoudaki, M.
Mitrakos, A.
Amenta, S.
Selenti, N.
Kanavakis, E.
Zafeiriou, D.
Kitsiou-Tzeli, S.
Fryssira, H.
Περιοδικό:
Pediatric Research
Εκδότης:
Nature Publishing Group
Λέξεις-κλειδιά:
ARHGAP11B protein; ARHGEF7 protein; ASTN1 protein; CHD5 protein; DOCK8 protein; EFNA2 protein; EHMT1 protein; F box protein; FBXO31 protein; forkhead transcription factor; FOX1 protein; FOXK2 protein; FREM1 protein; genomic DNA; MAP1LC3B protein; microtubule associated protein; PLCH2 protein; protein; RAB36 protein; RAC3 protein; RANBP1 protein; SKI protein; SLBP protein; transcription factor; transcription factor FOXP1; transcription factor Sox1; TRIM28 protein; unclassified drug; unindexed drug; WHSC1 protein; WHSC2 protein, Article; brain size; child; cohort analysis; comparative genomic hybridization; copy number variation; female; fluorescence in situ hybridization; gene deletion; gene duplication; gene locus; genetic analysis; genetic screening; genotype phenotype correlation; high resolution array comparative genomic hybridization; human; infant; karyotype; major clinical study; male; microarray analysis; microarray kit; microcephaly; newborn; nuclear magnetic resonance imaging; patient referral; preschool child; priority journal; syndromic microcephaly; comparative genomic hybridization; genetics; karyotyping; microcephaly; procedures; syndrome, Child; Cohort Studies; Comparative Genomic Hybridization; Female; Humans; Karyotyping; Male; Microcephaly; Syndrome
