Abnormal expression of the KLF8 (ZNF741) gene in a female patient with an X;autosome translocation t(X;21)(p11.2;q22.3) and non-syndromic mental retardation.

Non-syndromic X linked mental retardation (MRX) is a heterogeneous group of conditions in which all patients have mental retardation as the only constant phenotypic feature. We have identified a female patient with mental retardation and a balanced translocation involving chromosomes X and 21, t(X;21)(p11.2;q22.3). Physical mapping of the translocation breakpoint on the human X chromosome was performed using fluorescence in situ hybridisation. We have mapped the X chromosome breakpoint to a 21 kb DNA fragment upstream of the first exon of the KLF8 (ZNF741) gene in Xp11.21. We have subsequently shown that the KLF8 transcript is no longer detected in cells from the patient, although KLF8 expression is otherwise normally present in control lymphoblasts. Mutation screening of probands from 20 unrelated XLMR families linked to the proximal short arm of the human X chromosome failed to show any mutation in the coding region of the KLF8 gene.

Molecular characterization of a new human T-box gene (TBX22) located in xq21.1 encoding a protein containing a truncated T-domain.

We are conducting a systematic transcriptional mapping of the Xq12-q21 region of the human X chromosome in order to identify new genes potentially involved in X-linked mental retardation phenotypes. In silico analysis using the sequence of the genomic clones originating from this region of the human X chromosome allowed us to characterize a new gene belonging to the T-box family of transcriptional regulators. These genes were shown to be critical for proper development of both vertebrates and invertebrates. We show here that this new gene, called TBX22, is composed of seven exons spanning 8.7 kilobases of genomic DNA in Xq21.1. The TBX22 mRNA is 2099 base pairs long and encodes a 400-amino-acids protein containing a T-domain in its NH(2)-terminal region which has the unique feature of missing 20 amino-acids relative to the other known T-domains. TBX22 transcripts were exclusively found in a human fetal cDNA library and no homologous gene could be detected in the mouse genome. In addition, phylogenetic studies performed using all the known T-domain-containing proteins show that TBX22 is not directly related to any of them. These data indicate that TBX22 may be the first identified member of a new family of T-domain-containing proteins.