alpha1-Antitrypsin (PI) deficiency is a common autosomal recessive disorder associated with emphysema and liver disease, which may result from a wide spectrum of mutations causing a reduction of serum levels (deficient alleles) or a total lack of circulating protein (null alleles). We report two different alleles associated with the absence of isoelectric focusing banding patterns in Portuguese patients with emphysema. The first allele, Q0(ourém), results from the recurrence of the defining mutation of the Q0(mattawa) variant (L353fsX376) on a M3 normal background. The second allele, Q0(porto), has a novel G-->A mutation at position +1 of the intron IC (IVS1C+1G-->A), which restricts mononuclear phagocyte transcripts to mRNA species resulting from the direct splice of exon IA to exon II. The absence of this normal splice alternative in the liver, where PI is primarily synthesized, provides a basis for the pathogenic effects of this mutation.
Cantharidin is a poisonous substance secreted by blister beetles, including the ‘Spanish fly’. Historically, cantharidin was used as an aphrodisiac, vesicant and abortifacient. Symptoms of poisoning include gastrointestinal and genitourinary mucosal irritation along with renal dysfunction. We present the case of a reckless 23-year-old soldier who accepted the challenge of eating a beetle (Berberomeloe majalis). Six hours later he was admitted to the emergency room with abdominal pain, dysuria, gross haematuria with clots, hypotension, fever and renal insufficiency. With intravenous fluid therapy, he recovered clinically. Laboratory parameters returned to normal within 1 week.
α-1 Antitrypsin deficiency (AATD) caused by null alleles is associated with the total lack of protein and generally it translates into more severe clinical features of pulmonary disease. This is the case of Q0(Ourém) , a rare variant found in several families of Central Portugal caused by the L353fsX376 mutation. A total of 41 patients carrying at least one copy of Q0(Ourém) were evaluated for SERPINA1 levels, respiratory function values and lung parenchyma status (chest X-ray and computerized tomography scan). Q0(Ourém) haplotype background was characterized using seven microsatellites flanking SERPINA1 and Q0(Ourém) age was estimated by a statistical method relying on the decay of haplotype sharing at linked markers (DHSMAP). Homozygous patients showed a compromised lung function and extensive emphysema. SQ0(Ourém) , although having serum levels below the 11 µM threshold, did not necessarily result in signs of disease. MQ0(Ourém) were found to be a heterogeneous group, mainly composed of normal individuals. Eight Q0(Ourém) haplotypes were identified and the allele was estimated to have arisen 650 years ago. Q0(Ourém) was associated with mild to severe AATD and has a single origin, probably linked to the major Ourém settlements where the occurrence of severe AATD may not be explained by recent consanguinity.
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