Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019209 (hepatomegaly)
 5,798 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A report on 9 cases of infantile hepatopathy and cirrhosis of the liver respectively in cases of hereditary autosome-recessive alpha 1-antitrypsin deficiency (alpha 1-ATM). The genetic variants of the serum-protease-inhibitor (Pi) alpha 1-antitrypsin (alpha 1-AT) were examined by means of iso-electric focusing (Polyacrylamidgelen). The gene incidence was of the allel PiZ 0,0138 in the 868 blood donors from the Tyrol and was therefore within the range of the PiZ-frequencies seen in other Central-European populations. The other alleles PiM1, PiM2, PiM3, and PiS, point to the incidence of 0.7062, 0.1480, 0.1037, and 0.0225. The patients under observation (9) are homozygote PiZZ, the clinically healthy parents heterozygote PiZM. Risk of repetition in siblings of the patients is 25%. Early indicative symptoms are prolonged jaundice, acholic stools and hepatomegaly. Further developments are the fading of the hyperbilirubinaemia, temporary improvement in the pathological liver values, a freedom of symptoms for different lengths of time in each case, in the case of two patients, finally, decompensated cirrhosis of the liver and death in hepatic coma. The histological picture of the liver tissue shows PAS-positive storage granula in hepatozytes, intrahepatic hypoplasia of the bile duct, cholestasis as well as early cell necrobiosis, fibrosis and cirrhotic transformation. Course and severity of the liver complaint differ greatly, and are independent of the quantitative alpha 1-antitrypsin deficiency revealed, treatment is purely symptomatic.
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PMID:[Hereditary alpha 1-antitrypsin deficiency and infantile cirrhosis of the liver]. 676 50

Ataxia telangiectasia (A-T) is a neurodegenerative autosomal recessive disorder with the main characteristics of progressive cerebellar degeneration, sensitivity to ionizing radiation, immunodeficiency, telangiectasia, premature aging, recurrent sinopulmonary infections, and increased risk of malignancy, especially of lymphoid origin. Ataxia Telangiectasia Mutated gene, ATM, as a causative gene for the A-T disorder, encodes the ATM protein, which plays an important role in the activation of cell-cycle checkpoints and initiation of DNA repair in response to DNA damage. Targeted next-generation sequencing (NGS) was performed on an Iranian 5-year-old boy presented with truncal and limb ataxia, telangiectasia of the eye, Hodgkin lymphoma, hyper pigmentation, total alopecia, hepatomegaly, and dysarthria. Sanger sequencing was used to confirm the candidate pathogenic variants. Computational docking was done using the HEX software to examine how this change affects the interactions of ATM with the upstream and downstream proteins. Three different variants were identified comprising two homozygous SNPs and one novel homozygous frameshift variant (c.80468047delTA, p.Thr2682ThrfsX5), which creates a stop codon in exon 57 leaving the protein truncated at its C-terminal portion. Therefore, the activation and phosphorylation of target proteins are lost. Moreover, the HEX software confirmed that the mutated protein lost its interaction with upstream and downstream proteins. The variant was classified as pathogenic based on the American College of Medical Genetics and Genomics guideline. This study expands the spectrum of ATM pathogenic variants in Iran and demonstrates the utility of targeted NGS in genetic diagnostics.
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PMID:A novel pathogenic variant in an Iranian Ataxia telangiectasia family revealed by next-generation sequencing followed by in silico analysis. 2871 42

Metastatic pancreatic cancer (PC) is an aggressive malignancy, with most patients deriving benefit only from first-line chemotherapy. Increasingly, the recommended treatment for those with a germline mutation in a gene involved in homologous recombination repair is with a platinum drug followed by a poly (ADP-ribose) polymerase (poly adenosine phosphate-ribose polymerase [PARP]) inhibitor. Yet, this is based largely on studies of BRCA1/2 or PALB2 mutated PC. We present the case of a 44-year-old woman with ATM-mutated PC who achieved stable disease as the best response to first-line fluorouracil, leucovorin, irinotecan, and oxaliplatin, followed by progression on a PARP inhibitor. In the setting of jaundice, painful hepatomegaly, and a declining performance status, she experienced rapid disease regression with the nonplatinum regimen, gemcitabine plus nab-paclitaxel. Both physical stigmata and abnormal laboratory values resolved, imaging studies showed a reduction in metastases and her performance status returned to normal. Measurement of circulating tumor DNA for KRAS G12R by digital droplet polymerase chain reaction confirmed a deep molecular response. This case highlights that first-line treatment with a platinum-containing regimen followed by PARP inhibition may not be the best choice for individuals with ATM-mutated pancreatic cancer. Additional predictors of treatment response are needed in this setting.
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PMID:ATM-Mutated Pancreatic Cancer: Clinical and Molecular Response to Gemcitabine/Nab-Paclitaxel After Genome-Based Therapy Resistance. 3185 90