isolated gene in WBS/ mechanism similiar to CMT 1A - UK Research

[Guest guest]

From Eur J Hum Genet. Apr 21 2004

Isolation and characterisation of GTF2IRD2, a novel fusion gene and

member of the TFII-I family of transcription factors, deleted in

-Beuren syndrome.

Tipney HJ, Hinsley TA, Brass A, Metcalfe K, Donnai D, Tassabehji M.

1University of Manchester, Academic Unit of Medical Genetics and

Regional Genetic Service, St 's Hospital, Manchester, UK.

-Beuren syndrome (WBS) is a developmental disorder with

characteristic physical, cognitive and behavioural traits caused by a

microdeletion of approximately 1.5 Mb on chromosome 7q11.23. In total,

24 genes have been described within the deleted region to date. We have

isolated and characterised a novel human gene, GTF2IRD2, mapping to the

WBS critical region thought to harbour genes important for the cognitive

aspects of the disorder. GTF2IRD2 is the third member of the novel

TFII-I family of genes clustered on 7q11.23. The GTF2IRD2 protein

contains two putative helix-loop-helix regions (I-repeats) and an

unusual C-terminal CHARLIE8 transposon-like domain, thought to have

arisen as a consequence of the random insertion of a transposable

element generating a functional fusion gene. The retention of a number

of conserved transposase-associated motifs within the protein suggests

that the CHARLIE8-like region may still have some degree of transposase

functionality that could influence the stability of the region in a

mechanism similar to that proposed for Charcot-Marie-Tooth neuropathy

type 1A. GTF2IRD2 is highly conserved in mammals and the mouse ortholgue

(Gtf2ird2) has also been isolated and maps to the syntenic WBS region on

mouse chromosome 5G. Deletion mapping studies using somatic cell hybrids

show that some WBS patients are hemizygous for this gene, suggesting

that it could play a role in the pathogenesis of the disorder.