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)

We report a Japanese woman with 46,XX,dup(16)(p13.11p13.3), who closely resembled the phenotype of X-linked alpha-thalassemia/mental retardation syndrome (ATR-X, MIM # 301040). Although she never had alpha-thalassemia, she showed characteristic clinical features including severe mental retardation, characteristic facies and behavior. ATR-X is caused by mutations of the ATRX gene. Although the function of ATRX protein has remained unclarified, it is thought to be involved in the regulation of several genes. The only target gene identified so far is the alpha-globin gene at 16p13.3. Clinical similarity among patients with ATR-X and dup(16)(p13.11p13) may indicate that some target genes regulated by ATRX reside in the duplicated region between 16p13.11 and 16p13.3, and that these genes are abnormally upregulated in ATR-X differently from the alpha-globin gene.
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PMID:A woman with 46,XX,dup(16)(p13.11 p13.3) and the ATR-X phenotype. 1563 66

The phenotype of increased Hb A2 typical of beta-thalassaemia (beta-thal) carriers can be reduced to normal or borderline values because of the co-inheritance of a delta-globin gene (HBD, MIM #142000) mutation, which may lead to misinterpretation of diagnostic results. To know the spectrum of delta-globin mutations in the Portuguese population we performed a mutational analysis of the delta-globin gene in a group of 51 Portuguese beta-thal carriers presenting microcytosis, hypochromia and a normal/borderline Hb A2 level and in another group of 15 individuals suspected to have delta-globin structural abnormalities. The heterozygosity for the beta(+)IVS-I-6T-->C (HBB:c. 92+6T>C) mutation was the main cause for the mentioned atypical beta-thal carrier phenotype. Furthermore, eight individuals were double heterozygous for one common beta-thal mutation and the delta(+)Cd27G-->T mutation (Hb A2-Yialousa; HBD:c.82G>T). One of them also presented a novel delta-globin gene promoter mutation,-80G-->A (HBD:c.-130G>A), responsible for about 25% decrease of the promoter activity in transient expression assays. One the other hand, in the other group of 15 individuals suspected to have delta-globin structural abnormalities observed by biochemical methods, some known Hb A2 variants were identified - Hb A2' (HBD:c.49G>C), Hb A2-Babinga (HBD:c.410G>A), and Hb A2-Wrens (HBD:c.295G>A), and the novel Hb A2-Fogo [delta64(E8)(Gly-->Ser); (HBD:c.193G>A)]. This novel Hb A2 variant was observed segregating in linkage with Hb E (HBB:c.79G>A) in a three generation family. In conclusion, six different delta-globin mutations were found, being two of them new molecular defects. All delta-alleles identified were found linked to the expected beta-globin cluster haplotype. All mutations caused a low Hb A2 level and through this could lead to misdiagnosis when inherited together with a beta-thal allele.
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PMID:Mutational spectrum of delta-globin gene in the Portuguese population. 1791 81

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