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.

Pleural mesothelioma in a young male patient.

We present the case of a 33-year-old male patient suffering from lymphocytic pleural effusion, as a result of pleural mesothelioma. Mesothelioma is a malignant tumor of the pleura that is mainly caused by chronic exposure to asbestos fibers and more than 40 years of exposure are needed to develop the disease. Early studies on the relationship of asbestos and mesothelioma were issued in the 1960s. Fibers migrate from the parenchyma of the lung to the visceral pleura. It is widely known that asbestos is an oncogenic factor which can cause damage to DNA. A chest x-ray may reveal pleural effusion with or without pleural thickening, whereas a chest CT may also reveal pleural thickening, uniform and/or lobular. Specific tests, such as immunohistochemical staining, are used in order to help differential diagnosis. Extrapleural pneumonectomy is used as a therapeutic option which involves removal of the lung as well as both the visceral and parietal pleura, the affected part of the pericardium and diaphragm. Surgery should be followed up by radiotherapy and chemotherapy. The surgery may lead to a mean survival rate of approximately 9-21 months. The case presented underlines that in the event of pleural effusion with a lymphocyte type physicians should consider the possibility of a pleural mesothelioma during differential diagnosis, even in relatively young patients.