We identified a deletion of a gene encoding a subunit of RNA polymerases I and III, POLR1D, in an individual with Treacher Collins syndrome (TCS). Subsequently, we detected 20 additional... Show moreWe identified a deletion of a gene encoding a subunit of RNA polymerases I and III, POLR1D, in an individual with Treacher Collins syndrome (TCS). Subsequently, we detected 20 additional heterozygous mutations of POLR1D in 252 individuals with TCS. Furthermore, we discovered mutations in both alleles of POLR1C in three individuals with TCS. These findings identify two additional genes involved in TCS, confirm the genetic heterogeneity of TCS and support the hypothesis that TCS is a ribosomopathy. Show less
Dauwerse, J.G.; Dixon, J.; Seland, S.; Ruivenkamp, C.A.L.; Haeringen, A. van; Hoefsloot, L.H.; ... ; Wieczorek, D. 2011
Apparently balanced chromosome abnormalities are occasionally associated with mental retardation (MR). These balanced rearrangements may disrupt genes. However, the phenotype may also be caused by... Show moreApparently balanced chromosome abnormalities are occasionally associated with mental retardation (MR). These balanced rearrangements may disrupt genes. However, the phenotype may also be caused by small abnormalities present at the breakpoints or elsewhere in the genome. Conventional karyotyping is not instrumental for detecting small abnormalities because it only identifies genomic imbalances larger than 5-10 Mb. In contrast, high-resolution whole-genome arrays enable the detection of submicroscopic abnormalities in patients with apparently balanced rearrangements. Here, we report on the whole-genome analysis of 13 MR patients with previously detected balanced chromosomal abnormalities, five de novo, four inherited, and four of unknown inheritance, using Single Nucleotide Polymorphism (SNP) arrays. In all the cases, the patient had an abnormal phenotype. In one familial case and one unknown inheritance case, one of the parents had a phenotype which appeared identical to the patient's phenotype. Additional copy number variants (CNVs) were identified in eight patients. Three patients contained CNVs adjacent to one or either breakpoints. One of these patients showed four and two deletions near the breakpoints of a de novo pericentric inversion. In five patients we identified CNVs on chromosomes unrelated to the previously observed genomic imbalance. These data demonstrate that high-resolution array screening and conventional karyotyping is necessary to tie complex karyotypes to phenotypes of MR patients. (C) 2010 Elsevier Masson SAS. All rights reserved. Show less
