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This concise review summarizes the role of reduced ANXA5 expression through carriage of the M2/ANXA5 haplotype as a predisposing factor for various thrombophilia related obstetric complications. A revised ANXA5 ‘protective shield’ model is emphasized, where decreased coverage resulting of M2 carriage at placental villi could lead directly to the observed pathology and on the other hand through exposing of antiphospholipid antigenic determinants, to the development of antiphospholipid antibodies (aPL). The aPL then can further disrupt the ANXA5 protective shield. Available and prospective evidence for this revised model is discussed. Conclusions are made about the diagnostic implications of M2 carriage and possible therapeutic strategies with anticoagulants, proven successful in obstetric antiphospholipid syndrome (APS) treatment. [ABSTRACT FROM AUTHOR]

This is a family of three children, born to healthy Macedonian parents after uneventful pregnancies and delivery. The index child was an eight-year-old girl admitted for abdominal discomfort and distension: the spleen was 14cm below the costal margin (BCM), the liver 8cm BCM. No bone pain or pathology was reported. There was mild pancytopaenia (hemoglobin 11.2 gm/L; WBC counts 4.6 x 103, platelets 70 x 103). Liver function tests, renal ultrasound, bone scan, and a chest radiograph were within normal limits. Bone marrow analysis in this child and her two brothers ( 11 and 6.5 years old) revealed Gaucher cells. Both brothers had only mild anaemia, but the older brother had been splenectomized prior to diagnosis of GD1. Enzyme analysis revealed low activity (2.59, 1.62, and 2.55 nmol/h/mg protein, respectively); plasma chitotriosidase levels were also elevated. Genetic testing revealed homozygosity for the N370S/N370S mutation in all three siblings. In the absence of available enzyme replacement treatment (ERT), the girl was splenectomized. Removing an important immune organ (the spleen) introduces further risk for the patients. In addition, this does not solve the bone involvement characteristic for GD. ERT should be introduced for all GD1 patients in Macedonia. [ABSTRACT FROM AUTHOR]

Hereditary spastic paraplegia (HSP) is an extremely heterogeneous group of neurodegenerative disorders affecting the longest axons in the central nervous system. The most common genetic form accounting for about 40% of the autosomal-dominant HSP (ADHSP) cases is spastin gene, SPG4. We performed mutation screening of the spastin gene on 36 unrelated HSP patients from three different ethnic groups (Bulgarian, Turks and Gypsies) and found four new mutations and one already reported. The phenotype–genotype correlations in Bulgarian SPG4 patients showed a great difference in the age at disease onset between patients with missense mutations and those harboring deletions and splice-site mutations. Our study is the first to present corroborative clinical data in favor of the general hypothesis that the clinical course of the disease is related to the type of the spastin mutation. The clinical and genealogical findings in Bulgarian SPG4 patients suggest that a positive family history for inheritance as an autosomal-dominant trait is a strong indication for spastin mutation screening. [ABSTRACT FROM AUTHOR]

Georgieva B, Todorova A, Tournev I, Mitev V, Kremensky I. C283Y gamma-sarcoglycan gene mutation in the Bulgarian Roma (Gypsy) population: prevalence study and carrier screening in a high-risk community.Limb-girdle muscular dystrophy type 2C (LGMD2C) is caused by mutations in thegamma-sarcoglycangene where a founder Gypsy mutation C283Y was detected. The Bulgarian Gypsy LGMD2C patients, as the Gypsy patients from other countries, were found to be homozygous for this mutation. Considering the large number of Gypsies in Bulgaria and the high percent of consanguinity and endogamy a raised carrier frequency of the C283Y mutation was expected especially in North-Eastern Bulgaria where most of the patients originate from. Here, we present the precise geographic distribution of the C283Y mutation in the general Roma population from the whole Bulgarian territory by determining the carrier frequency of the mutation in dry blood newborn samples. Our results show that the geographic distribution of this founder mutation and the disease are not geographically restricted only among Gypsies from North-Eastern Bulgaria. We stress upon the regions with detected high carrier and/or disease frequency and upon the results from the performed carrier screening on volunteers in one of these regions. The ongoing carrier-screening programs in isolated Gypsy groups would be of a great benefit for the genetic prophylaxis of the disease. Such regions should be with priority in the Bulgarian healthcare system for performing a carrier-screening program. [ABSTRACT FROM AUTHOR]

Presents a letter to the editor about mutation in Wilson disease gene.

A letter to the editor about a Bulgarian Roma family with Wilson's disease in two consecutive generations is presented.