Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038002 (splenomegaly)
 9,873 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We describe moderate hyperbilirubinemia in a 28-year-old man who suffered from gallstones and splenomegaly, with combined disorders of hereditary spherocytosis (HS) and Gilbert's syndrome (GS). Since it is difficult to diagnose HS in the absence of signs of anemia, we evaluated both the genetic mutation in the UGT1A1 gene and abnormalities in the erythrocyte membrane protein; the former was heterozygous for a UGT1A1 allele with three mutations and the latter was partially deficient in ankyrin expression. This is the first report of the concomitance of HS and GS with three heterozygous mutations [T-3279G, A (TA)7TAA, and G211A] in the UGT1A1 gene.
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PMID:A case of concomitant Gilbert's syndrome and hereditary spherocytosis. 2092 16

Hereditary spherocytosis is a congenital red blood cell disorder. Typical clinical manifestations include anemia, jaundice and splenomegaly, which overlap with the thalassemia phenotype. Therefore, in high prevalence thalassemia regions, hereditary spherocytosis cases are often misdiagnosed. Here, a case once diagnosed as thalassemia, based on preliminary clinical examinations, underwent genetic testing in our laboratory, where analysis of globin gene mutations proved negative. We conducted both clinical and genetic analyses on the patient and his family. We collected clinical data, performed erythrocyte membrane protein analysis by SDS-PAGE and sequenced the ANK1 gene. We also investigated pathogenic mechanisms through cDNA sequencing and literature studies. From patient clinical data, we diagnosed the patient with moderate to severe hereditary spherocytosis, rather than thalassemia. SDS-PAGE data showed that Ankyrin protein expression was reduced. Sequencing of genomic DNA identified a frameshift mutation (ANK1:c.2394_2397del CAGT). cDNA sequencing showed that the expression of a mutant allele was significantly decreased. Our study corrected a clinical misdiagnosis and confirmed the diagnosis of hereditary spherocytosis in this patient. Identification of such causative mutations is important for accurate downstream patient therapy and is critically important for the prevention/detection of another affected birth. Additionally, the disruption of mRNA transcribed from the mutant allele resulted in a significant reduction in Ankyrin expression and was speculatively considered the pathogenic mechanism behind this mutation.
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PMID:A tetranucleotide deletion in the ANK1 gene causes hereditary spherocytosis; a case of misdiagnosis. 3166 44