Identification of critical regions for clinical features of distal 10q deletion syndrome

• Published in: Clinical genetics Vol. 76; no. 1; pp. 54 - 62
• Main Authors: Yatsenko, SA, Kruer, MC, Bader, PI, Corzo, D, Schuette, J, Keegan, CE, Nowakowska, B, Peacock, S, Cai, WW, Peiffer, DA, Gunderson, KL, Ou, Z, Chinault, AC, Cheung, SW
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.07.2009; Wiley-Blackwell
• Subjects: Adult; array comparative genomic hybridization; Biological and medical sciences; Child; Child, Preschool; Chromosome Deletion; chromosome rearrangement; Chromosomes, Human, Pair 10 - genetics; Classical genetics, quantitative genetics, hybrids; critical region; deletion 10q; DOCK1 gene; Female; Fundamental and applied biological sciences. Psychology; General aspects. Genetic counseling; Genetic disorders; Genetics of eukaryotes. Biological and molecular evolution; Genomics; Genotype & phenotype; genotype-phenotype correlation; Human; Humans; Infant, Newborn; Karyotyping; Male; Medical genetics; Medical sciences; Molecular and cellular biology; Pathology; Syndrome; Chromosomal aberration; Genetic mapping; Human; Correlation; Typing; DOCK1 gene; genotype-phenotype correlation; Critical region; chromosome rearrangement; Genotype; Identification; Chromosome C10; Syndrome; Symptomatology; Phenotype; Gene; Comparative genomic hybridization; array comparative genomic hybridization; Distal; Deletion; deletion 10q; Genetics
• ISSN: 0009-9163; 1399-0004
• DOI: 10.1111/j.1399-0004.2008.01115.x

Array comparative genomic hybridization studies were performed to further characterize cytogenetic abnormalities found originally by karyotype and fluorescence in situ hybridization in five clinical cases of distal 10q deletions, including several with complex cytogenetic rearrangements and one with a partial male‐to‐female sex‐reversal phenotype. These results have enabled us to narrow the previously proposed critical regions for the craniofacial, urogenital, and neuropsychiatric disease‐related manifestations associated with distal 10q deletion syndrome. Furthermore, we propose that haploinsufficiency of the DOCK1 gene may play a crucial role in the pathogenesis of the 10q deletion syndrome. We hypothesize that alteration of DOCK1 and/or other genes involved in regulation and signaling of multiple pathways can explain the wide range of phenotypic variability between patients with similar or identical cytogenetic abnormalities.