Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0039730 (thalassemia)
 10,305 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

SOX proteins are transcription factors that are characterized by a common DNA-binding motif known as the HMG domain. We describe the 5. 4-kb human SOX8 gene that codes for a 446-amino-acid protein and that is expressed strongly in brain and less abundantly in other tissues. SOX8 shows an overall identity of 47% to SOX9 and SOX10. The latter two possess a C-terminal transactivation domain, whereas in SOX8, this domain is located in the central part of the protein. We have mapped SOX8 within 700 kb of the telomeric repeats of band 16p13.3. Hemizygosity for 1 Mb from this region causes the ATR-16 syndrome characterized by alpha-thalassemia and mental retardation. We show that SOX8 is deleted in an ATR-16 patient, and from its location, we deduce that it should be deleted in all previously described cases. Thus, SOX8 is a good candidate gene contributing to the mental retardation phenotype seen in ATR-16 patients.
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PMID:The SOX8 gene is located within 700 kb of the tip of chromosome 16p and is deleted in a patient with ATR-16 syndrome. 1066 50

SOX proteins form a large family of transcription factors related by a DNA-binding domain known as the HMG box. Some 30 Sox genes have been identified in mammals and orthologues have been found in a wide range of other metazoans. Sox genes are highly conserved and are known to play important roles in embryonic development, including roles in gonadal, central nervous system, neural crest and skeletal development. Several SOX genes have been implicated in human congenital diseases. We report here the isolation of Sox8 and its characterisation in mice and humans. This gene has a remarkably similar primary structure and genomic organisation to the campomelic dysplasia gene SOX9 and the Waardenburg-Shah syndrome gene SOX10. SOX8 protein is able to bind to canonical SOX target DNA sequences and activate transcription in vitro through two separate trans -activation regions. Further, Sox8 is expressed in the central nervous system, limbs, kidneys, gonads and craniofacial structures during mouse embryo development. Sox8 maps to the t complex on mouse chromosome 17 and to human chromosome 16p13.3, a region associated with the microphthalmia-cataract syndrome CATM and the alpha-thalassemia/mental retardation syndrome ATR-16.
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PMID:Cloning and characterisation of the Sry-related transcription factor gene Sox8. 1068 44

An 8-year-old Caucasian girl presented with mild dysmorphic features and intellectual disability (ID) affecting multiple spheres. Dysmorphisms included a high forehead with up-slanting palpebral fissures, prominent nasal root and bridge, flattened maxilla, high-arched palate, and anterior frenulum. Structural brain anomalies included reduced periventricular white matter volume and thin corpus callosum. The presence of HbH bodies and her clinical presentation raised suspicion for autosomal alpha-thalassemia mental retardation syndrome (ATR-16). Whole-genome array analysis at 1 Mb resolution was performed, which revealed a sub-microscopic loss of 16p involving clones RP11-344L6 at 0.1 Mb, RP1-121I4 at 0.2 Mb and RP11-334D3 at 1 Mb. FISH confirmed deletion (del) of the terminal clone (RP1-121I4) on 16pter, which was de novo in origin. The more proximal clone RP11-334D3 (at 1 Mb) showed diminished FISH signal intensity on one of the homologues, suggesting that one breakpoint occurred within this clone. Quantitative PCR (qPCR) confirmed a de novo deletion encompassing SOX8 (at 0.97 Mb). ATR-16 is characterized by ID with mild, nonspecific dysmorphic features, and is associated with terminal del16p (MIM No. 141750). Cases of isolated monosomy for 16p are rarely described; such descriptions help to delineate the syndrome in the absence of confounding karyotypic anomalies. We describe detailed molecular cytogenetic and clinical findings relating to a subject with ATR-16.
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PMID:Phenotype-genotype characterization of alpha-thalassemia mental retardation syndrome due to isolated monosomy of 16p13.3. 1807 5