Interstitial microdeletions in the proximal region of the long arm (q) of chromosome 6 are rare. There have been previous studies that show a correlation between a candidate gene SIM1 located at 6q16.3 and Prader-Willi syndrome (PWS)-like clinical manifestations such as hypotonia and developmental delay. Machida et al. present 12 patients (6 females and 6 males), ranging in ages 1 to 21 years old with interstitial deletions involving proximal segment of the long arm of chromosome 6. Deletion sizes ranged from as 4.4 Mb (Patient 6) to 37.8 Mb (Patient 4). All patients exhibited developmental delay, but its extent significantly varied. Patients 4 and 7 share a deleted region that includes the gene SIM1, which has been linked to obesity and PWS-like features in loss of function variants in previous studies. Patient 7 exhibits these manifestations, but Patient 4 with a larger deletion size, showed a more severe developmental delay. Patient 4 also has an overlapping deleted region with Patients 5 and 6 which includes the gene ZNF292; haploinsufficiency of ZNF292 is related to intellectual developmental disorder. The shortest region of overlapping deletions was observed in Patients 2, 3, and 4—including the PHIP gene, which is suggested to cause Chung-Jansen syndrome, a disorder described by a global developmental delay in infants, impaired intellectual development, behavioral abnormalities, dysmorphic features, and obesity. The authors also suggest that PHIP haploinsufficiency contributes to the neurodevelopmental delay observed in these three patients. The gene KCNQ5 located at 6q13 is also suggested to be related to the clinical features of this study; loss of this gene may explain the developmental delay observed in Patient 2 as its loss of function variants are related to intellectual developmental disorder. Finally, NUS1 deletion at 6q22 found in Patients 10 and 11 has previously been related to a pathogenic mechanism for intellectual developmental disorder. In summary, among the genes located in the proximal segments of 6q, only five genes (SIM1, ZNF292, PHIP, KCNQ5, and NUS1) were considered by the authors to be related to developmental delay observed in the 12 patients observed in this study.
Machida et al. “Interstitial deletions in the proximal regions of 6q: 12 original cases and a literature review”. “Intractable & Rare Diseases Research” 2022, v.11:3.
Chromosome Disorder Outreach Inc. medical geneticist and medical advisor Dr. Iosif Lurie M.D. Ph.D examines newly published research studies to locate the most important and relevant for our members. Synopses of these articles are then posted to our website’s research pages. For more information on any article please contact firstname.lastname@example.org