Neurofibromatosis type 1 is a tumor predisposition syndrome inherited in autosomal dominant manner. Besides the intragenic loss-of-function mutations in NF1 gene, large deletions encompassing the NF1 gene and its flanking regions are responsible for the development of the variable clinical phenotype. These large deletions titled as NF1 microdeletions lead to a more severe clinical phenotype than those observed in patients with intragenic NF1 mutations. Around 5-10% of the cases harbor large deletion and four major types of NF1 microdeletions (type 1, 2, 3 and atypical) have been identified so far. They are distinguishable in term of their size and the location of the breakpoints, by the frequency of somatic mosaicism with normal cells not harboring the deletion and by the number of the affected genes within the deleted region. In our study genotype-phenotype analyses have been performed in 17 mostly pediatric patients with NF1 microdeletion syndrome identified by multiplex ligation-dependent probe amplification after systematic sequencing of the NF1 gene. Confirmation and classification of the NF1 large deletions were performed using array comparative genomic hybridization, where it was feasible. In our patient cohort 70% of the patients possess type-1 deletion, one patient harbors type-2 deletion and 23% of our cases have atypical NF1 deletion. All the atypical deletions identified in this study proved to be novel. One patient with atypical deletion displayed mosaicism. In our study NF1 microdeletion patients presented dysmorphic facial features, macrocephaly, large hands and feet, delayed cognitive development and/or learning difficulties, speech difficulties, overgrowth more often than patients with intragenic NF1 mutations. Moreover, neurobehavior problems, macrocephaly and overgrowth were less frequent in atypical cases compared to type-1 deletion. Proper diagnosis is challenging in certain patients since several clinical manifestations show age-dependency. Large tumor load exhibited more frequently in this type of disorder, therefore better understanding of genotype-phenotype correlations and progress of the disease is essential for individuals suffering from neurofibromatosis to improve the quality of their life. Our study presented additional clinical data related to NF1 microdeletion patients especially for pediatric cases and it contributes to the better understanding of this type of disorder.

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Romani people are a significant minority in Europe counting about 10 million individuals scattered throughout the continent. They are a migratory group originating from Northwestern India. Their exodus from India occurred approximately 1000–1500 years ago. The migration route of the Romani people was reconstructed with the help of cultural anthropology, linguistics and historical records. Their migration made them through Central Asia, Middle East and the Caucasus region, prior to the arriving into Europe. Yet the significance of these regions, especially of the Caucasus, in Roma ancestry was a rather neglected topic. Contribution of the Caucasus and further affected regions to the ancestry of Roma was investigated based on genome-wide autosomal marker data. 158 European Roma samples and 41 populations from the Caucasus region, from Middle East, Central Asia and from South Asia were considered in our tests. Population structure and ancestry analysis algorithms were applied to investigate the relationship of Roma with these populations. Identical by descent DNA segment analyses and admixture linkage disequilibrium based tests were also applied. Our results suggest that the Caucasus region plays also a significant role in the genetic legacy of Romani people besides the main sources, Europe and South Asia, previously investigated by other population genetic studies. The Middle East and Central Asia seems slightly less important but far from negligible in connection with the sources of Roma ancestry. Our results point out that the Caucasus region and altogether the area of the Caspian and Black Seas had a significant role in the migration of Romani people towards Europe and contributed significantly to the genetic legacy of Roma rival to the European and Indian main sources.

The advances in molecular genetic methods has lead to the discovery of the genetic alterations that underlie the etiology of most diseases previously held to be idiopathic. Targeted genetic examination of a pediatric male patient showing a normal intellect, an extended area of skin hypopigmentation, and suffering from generalized epilepsy displaying a switch in epilepsy syndrome during the course of the disease towards a neurocutaneous syndrome was unsuccessful. Whole-exome sequencing identified a heterozygous missense mutation in a potassium chloride cotransporter gene, which together with the phenotype underscores the diagnosis of an epilepsy syndrome known in the literature as idiopathic generalized epilepsy type 14. Orv Hetil. 2019; 160(21): 835–838.

Genome-wide genotype data from 48 carefully selected population samples of Transylvania-living Szeklers and non-Szekler Hungarians were analyzed by comparative analysis. Our analyses involved contemporary Hungarians living in Hungary, other Europeans, and Eurasian samples counting 530 individuals altogether. The source of the Szekler samples was the commune of Korond, Transylvania. The analyzed non-Szekler Hungarian samples were collected from villages with a history dating back to the era of the Árpád Dynasty. Population structure by principal component analysis and ancestry analysis also revealed a great within-group similarity of the analyzed Szeklers and non-Szekler Transylvanian Hungarians. These groups also showed similar genetic patterns with each other. Haplotype analyses using identity-by-descent segment discovering tools showed that average pairwise identity-by-descent sharing is similar in the investigated populations, but the Korond Szekler samples had higher average sharing with the Hungarians from Hungary than non-Szekler Transylvanian Hungarians. Average sharing results showed that both groups are isolated compared to other Europeans, and pointed out that the non-Szekler Transylvanian Hungarian inhabitants of the investigated Árpád Age villages are more isolated than investigated Szeklers from Korond. This was confirmed by our autozygosity analysis as well. Identity-by-descent segment analyses and 4-population tests also confirmed that these Hungarian-speaking Transylvanian ethnic groups are strongly related to Hungarians living in Hungary.