Informational summary of chromosome 8 (8p and 8q) disorders — deletions and trisomy. Overview of clinical characteristics.
Summary of meeting held on May 21-23, 2010 on 8p23 deletions, with emphasis on inv dup del 8p. Report summarizes some key presentations: background on 8p deletions, behavioral aspects, Q&A session. Identifies several key genes that may be involved:
In del 8p23.1:
In the core 8p23.1 deletion region (yellow in right slide b, page i) there are roughly 57 genes that are reduced from two copies to one copy. For many genes, one copy is enough and this does not matter, but for others it does. We are still at the early stages but there are now some ‘candidate’ genes for some of the phenotypic features that people may have (slides below and above left):
TNKS (‘tinks’) – TNKS may be one of the causes of behavioural difficulties and is deleted in most of the terminal and interstitial deletions of 8p23.1.
SOX7 – SOX7 may be related to the developmental delay and possibly heart defects (see GATA4 below) and is deleted in most of the terminal and interstitial deletions of 8p23.1.
GATA4 – We are confident that the GATA4 gene causes the heart problems because heart defects are found in people with mutations of just this gene alone. Because SOX7 is part of the same pathway of genes that control the development of the heart as GATA4, SOX7 may provide an additional risk of developing heart disease as both genes are normally deleted in the terminal and interstitial deletions of 8p23.1. However, as a word of caution, not everyone has a heart defect even when both genes are deleted and therefore reduced to a single copy.
Although there are 57 genes in the core yellow interstitial deletion region, only five or six more genes are reduced to a single copy by deletions that include the red terminal region. Among these is: MCPH1 – MCPH1 is the microcephalin gene that is believed to have
had a role in the evolution of head size in humans and has been tentatively linked with the autistic features present in some children. However, this gene is only deleted in terminal 8p23.1 deletions (and inv dup del(8s)) and, as far as we know, is not affected by interstitial
deletions of 8p23.1.
Key genes in inv dup del 8p:
MCPH1 – as above, MCPH1 has been tentatively associated with autistic features but, while deleting a copy might be expected to give rise to a smaller head, microcephaly (small head size) is not a feature that all the children have. Duplications including MCPH1 have also been associated with epilepsy but MCPH1 is not duplicated in deletions of 8p23.1 or inv dup del 8.
STMN4 – STMN4 is duplicated in most inv dup del 8 and may be associated with behaviour and autistic spectrum disorders.
DPYSL2 – DPYSL2 is also duplicated in most inv dup del 8s and may be involved with self harm as a related gene on the X chromosome is known to be associated with self harm in children with Lesch-Nyhan syndrome.
Chromosome Disorder Outreach (CDO). (1994). Chromosome 8 Chapter. Chromosome Disorder Outreach Library https://chromodisorder.org/wp-content/uploads/2017/08/8ChromosomeChapter.pdf