Partial monosomy of 11q22.2q22.3 including the SDHD gene in individuals with developmental delay2015-03-09 00:01:12
American Journal of Medical Genetics, Part A; 3 MAR 2015; DOI:10.1002/ajmg.a.36956
Krishna Yelavarthi, Huong Cabral, Golder N. Wilson, Luis Rohena, Hiba Risheg, Andrea Penton, Justin Schleede, Rachel D. Burnside
Deletions in the middle portion of 11q are not as well described in the literature as terminal 11q deletions that result in Jacobsen syndrome. One confounding factor in the older literature is that the G-banding pattern of 11q13q21 is very similar to 11q21q23. The advent of fluorescence in situ hybridization and later microarray technologies have allowed for a better resolution of many of these deletions, but genotype-phenotype correlations are still difficult since these deletions are rare events. We present five individuals who presented with developmental delays with de novo 11q22.2q23.3 deletions. Deletions were observed by standard G-banded chromosome analysis with clarification of breakpoints and gene content by SNP microarray analysis. Of note, all individuals had identical distal breakpoints. All deletions include SDHD, which is implicated in hereditary paraganglioma/pheochromocytoma, for which the patients will need to be monitored in adulthood. In spite of the large deletions of 8.6 Mb (Patients 1 and 3), 13.98 Mb (Patient 2), and 12.6 Mb (Patients 4 and 5) all patients show somewhat mild intellectual disability and dysmorphism.
Deletions of distal 11q resulting in Jacobsen syndrome are well described, with features that include growth restriction, cognitive disability, dysmorphic facial features, cardiac defects, and thrombocytopenia or pancytopenia. The critical gene(s) for these features has not been precisely identified to date, and indeed many phenotypic features may be due to the combined effects of haploinsuf®ciency of multiple genes, asmany deletions are microscopically visible.
More proximal deletions of 11q are less well described, and older literature without molecular techniques such as FISH and microarray studies to precisely identify the region deleted is complicated by the fact that the G-banding pattern of 11q13q21 is very similar to 11q21q2. For these reasons, there is little consistency in the reported phenotype of individuals with interstitial 11q deletions, aside from varying degrees of developmental delays and intellectual disability.
We present five individuals with microscopically visible deletions of the middle portion of 11q for whom SNP microarray was utilized to re®ne the deletion breakpoints. All individuals presented
with developmental delays and mildly dysmorphic features, and two presented with anxiety. In addition, the gene, SDHD is encompassed in all deletions. This gene is implicated in paragangliomas/
pheochromocytomas for which the patients will have to undergo lifelong monitoring.
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SDHD gene | microarray | developmental delay | 11q | deletion