Chromosome 8p abnormalities studied in a group of individuals – 8p deletion, inversions and duplications.
The short arm of chromosome 8 includes several low copy repeat regions that predisposes to a non-allelic homologous recombination. As a result structural abnormalities of this region are much more frequent than for similar size segments of other chromosomes. The main types of deletions are “distal” 8p deletions (affecting ~ 6.5 Mb from the distal end of 8p), “proximal + distal” deletions (affecting ~10.5 Mb segment from the distal end of 8p), and “proximal” deletions (basically between 9.5 and 11.5 Mb from the distal end). Some patients have a combination of distal 8p deletions with inverted duplications of the more proximal segment, involving at least segment between 12.5 and 23.5 Mb (but usually much larger area, sometimes up to centromeric zone). This combination called invdupdel(8p) seems to be unique for this chromosome. All these variants have been reported in the literature, but the authors decided to compare manifestations in different groups based on large cohort of patients. They enrolled 97 individuals with different forms of 8p abnormalities only 2 of them have been previously reported. The patients were from different centers in USA (53), United Kingdom (14) and other European countries. The largest group (49 patients) had sn invdupdel(8p) variant. The study showed that the patients in all groups revealed developmental delay. The age of sitting unsupported, the age of first words and the age of walking was significantly increased in patients with invdupdel(8p) in comparison with all the deletion groups. At the same time not a single person in the invdupdel(8p) group was obese or overweight, although it was very common for patients in all the deletion groups. Dysmorphic features are usually mild and non-diagnostic. A significant number of patients with “proximal” (and “proximal + distal”) deletions had microcephaly, although it was found in only 4% of the invdupdel(8p) group. Autism and attention deficit hyperactivity disorder were noted almost exclusively in patients with deletions. Congenital heart defects were the most common internal defect reported in 2/3 of invdupdel(8p) patients and in almost all patients with “proximal” or “proximal + distal” deletions, but very rarely found in the “distal” deletion group. Constipation and gastroesophageal reflux were frequent in all sub-groups. The loss of the GATA4 gene is considered to be the main factor causing heart defects in patients with 8p abnormalities. However heart defects in invdupdel(8p) patients were relatively minor compared with individuals with “pure” deletions involving GATA4.
Okur V. et al. “Clinical and genomic characterization of 8p cytogenomic disorders”. “Genetics in Medicine” 2021, online ahead of print.
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