Clinical utility gene card for: deletion 22q13 syndrome

K Phelan, C Betancur - European Journal of Human Genetics, 2011 - nature.com
K Phelan, C Betancur
European Journal of Human Genetics, 2011nature.com
1.5 Mutational spectrum Phelan-McDermid syndrome can result from simple 22q13
deletions, ring chromosomes and unbalanced translocations. 1–5 The deletions are
extremely variable in size, ranging from 95kb to 9Mb. The gene responsible for the core
neurological features is SHANK3, which has been found to be mutated in patients with
autism spectrum disorders and intellectual disability. 6–9 55% de novo deletion 22q13. 3 of
the paternally derived chromosome 20% de novo deletion 22q13. 3 of the maternally …
1.5 Mutational spectrum Phelan-McDermid syndrome can result from simple 22q13 deletions, ring chromosomes and unbalanced translocations. 1–5 The deletions are extremely variable in size, ranging from 95kb to 9Mb. The gene responsible for the core neurological features is SHANK3, which has been found to be mutated in patients with autism spectrum disorders and intellectual disability. 6–9
55% de novo deletion 22q13. 3 of the paternally derived chromosome 20% de novo deletion 22q13. 3 of the maternally derived chromosome 10% paternal structural rearrangement 10% maternal structural rearrangement 4% de novo unbalanced rearrangement o1% mutations within SHANK3 gene (only a small number of studies have sequenced SHANK3, so the frequency may be underestimated). 6–10 Deletions of 22q13, not including the SHANK3 gene, have been reported in two unrelated individuals with Phelan-McDermid syndrome. 11
1.6 Analytical methods Chromosome analysis, FISH, array CGH, MLPA and DNA sequencing. Conventional cytogenetics is usually normal except for cases resulting from unbalanced translocations (24%). Small terminal or interstitial deletions of 22q13 will not be detected by FISH unless this region of chromosome 22 is targeted by probes specific for SHANK3 or other loci within the deleted region.
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