Alpha1-antitrypsin deficiency in Greece: Focus on rare variants.

PURPOSE: A1Antitrypsin deficiency (AATD) pathogenic mutations are expanding beyond the PI*Z and PI*S to a multitude of rare variants. AIM: to investigate genotype and clinical profile of Greeks with AATD. METHODS: Symptomatic adult-patients with early-emphysema defined by fixed airway obstruction and computerized-tomography scan and lower than normal serum AAT levels were enrolled from reference centers all over Greece. Samples were analyzed in the AAT Laboratory, University of Marburg-Germany. RESULTS: Included are 45 adults, 38 homozygous or compound heterozygous for pathogenic variants and 7 heterozygous. Homozygous were 57.9% male, 65.8% ever-smokers, median (IQR) age 49.0(42.5-58.5) years, AAT-levels 0.20(0.08-0.26) g/L, FEV1(%predicted) 41.5(28.8-64.5). PI*Z, PI*Q0, and rare deficient allele's frequency was 51.3%, 32.9%,15.8%, respectively. PI*ZZ genotype was 36.8%, PI*Q0Q0 21.1%, PI*MdeficientMdeficient 7.9%, PI*ZQ0 18.4%, PI*Q0Mdeficient 5.3% and PI*Zrare-deficient 10.5%. Genotyping by Luminex detected: p.(Pro393Leu) associated with MHeerlen (M1Ala/M1Val); p.(Leu65Pro) with MProcida; p.(Lys241Ter) with Q0Bellingham; p.(Leu377Phefs*24) with Q0Mattawa (M1Val) and Q0Ourem (M3); p.(Phe76del) with MMalton (M2), MPalermo (M1Val), MNichinan (V) and Q0LaPalma (S); p.(Asp280Val) with PLowell (M1Val); PDuarte (M4), YBarcelona (p.Pro39His). Gene-sequencing (46.7%) detected Q0GraniteFalls, Q0Saint-Etienne, Q0Amersfoort(M1Ala), MWürzburg, NHartfordcity and one novel-variant (c.1A>G) named Q0Attikon.Heterozygous included PI*MQ0Amersfoort(M1Ala), PI*MMProcida, PI*Mp.(Asp280Val), PI*MOFeyzin. AAT-levels were significantly different between genotypes (p = 0.002). CONCLUSION: Genotyping AATD in Greece, a multiplicity of rare variants and a diversity of rare combinations, including unique ones were observed in two thirds of patients, expanding knowledge regarding European geographical trend in rare variants. Gene sequencing was necessary for genetic diagnosis. In the future the detection of rare genotypes may add to personalize preventive and therapeutic measures.

Unusual case of pulmonary hypertension.

Truly reversible pulmonary hypertension is rare. Acquired systemic arteriovenous (A-V) fistulas following spinal surgery (laminectomy) are a less recognized cause of secondary pulmonary hypertension. We describe a patient who presented with symptoms and clinical evidence of pulmonary hypertension and underwent endovascular correction of an acquired A-V fistula, which led to improvement according to clinical and noninvasive hemodynamic criteria.

Combined carcinoid-adenocarcinoma tumour of the anal canal.

The concurrence of carcinoid admixed with adenocarcinoma in the gastrointestinal tract is an unusual phenomenon that has been reported in the oesophagus, stomach, small intestine, appendix, colon and rectum. These mixed or 'composite' tumours seem to be derived from a multipotential stem cell capable of bidirectional differentiation and have a worse prognosis than ordinary adenocarcinoma. Chromogranin-A staining has increased the diagnostic yield for detecting these tumours and provides information for perioperative management and long-term prognosis. We describe a patient who presented to our department due to painful defecation. Sigmoidoscopy demonstrated a mass in the anal canal. Histology revealed that the tumour was a mixed carcinoid-adenocarcinoma neoplasm. To our knowledge, this is the first report in the English literature of a composite tumour of the anal canal.