Development of Genetics in the World and in Croatia – Forty Years of the Croatian Society of Human Genetics of the Croatian Medical Association

Resulting from several basic scientific disciplines, genetics has made impressive progress in the last century by discoveries of the heredity rules and genome structure, and by identification of the genes that determine the occurrence and characteristics of human diseases. In Croatia, the development of genetics began in the middle of the past century by the pioneering work of clinicians and basic scientists, which resulted in significant development of this scientific discipline that has quickly found its practical application in clinical genetics-cytogenetics, molecular genetics and prenatal diagnosis. The rapid advancement of technology and knowledge of genetics in recent decades has led to the development of genomics and related disciplines, entering the revolutionary new era of personalized medicine. Currently, much more data can be collected than interpreted. The data of electronic medical records, genomics, epigenetics, proteomics, metabolomics and microbiomics should be integrated and interpreted at the level of individual genome. Extensive use of new information will open a range of ethical issues that we must face timely. It is expected that in the forthcoming years, we will be able to learn more about genetics than what we have learned throughout the history of medicine. We must be prepared to welcome this new knowledge, reflecting on the positive and negative aspects of the latest achievements in the field of genetics. We hope that the experts dealing with human genetics in Croatia will successfully continue their work to enable practical application of the latest achievements in genetics, expanding our understanding of the concept of health and disease

Novel duplication on chromosome 16 (q12.1-q21) associated with behavioral disorder, mild cognitive impairment, speech delay, and dysmorphic features: case report

We report on the 10-year follow-up and clinical, cytogenetic, and molecular investigation of a girl admitted for evaluation because of speech delay, learning difficulties, aggressive behavior, and dysmorphic facial features that included high forehead, round face, epicanthic folds, low-set dysplastic ears, flat nasal bridge, long flat philtrum, thin upper lip, small mouth, and short neck. The analysis of high-resolution GTG- and CTG-banding chromosomes suggested a de novo direct duplication of 16q12-q21 region and fluorescence in situ hybridization analysis with whole-chromosome specific 16 probe confirmed that the duplicated genetic material originated from the chromosome 16. Subsequently, array-based comparative genomic hybridization analysis with a ≈ 75 kb resolution showed a 9.92 Mb gain on the long arm of chromosome 16 at bands q12.1 through q21. To the best of our knowledge, this is the first case of duplication 16q12.1q21 described in literature. Several genes within the duplicated region are possibly correlated with clinical features present in our patient. Clinical and cytogenetic findings were compared with the small number of reported patients with pure duplications 16q, partially overlapping the one in our patient. Clinical phenotype seems to be distinctive between the proximal-intermediate and intermediate-distal regions of the long arm of the chromosome 16. In particular, we observed a set of dysmorphic features that could present a characteristic dup 16q11.2-q13 phenotype. The present study illustrates the advantages of an integrative approach using both conventional and molecular techniques for the precise characterization and genotype-phenotype correlation in patients with dysmorphism, behavioral problems, and learning difficulties

Screening of Patients at Risk for 22q11 Deletion

The aim of this study was to determine whether deletion 22q11.2 studies should become a part of a standardized diagnostic workup for selected groups of at risk patients. We prospectively investigated four cohorts of unselected patients referred because of: 1) congenital heart defect (CHD), 2) palatal anomalies, 3) hypocalcaemia, 4) dysmorphic features suggestive of del 22q11.2. Fluorescence in situ hybridization analysis revealed deletion 22q11.2 in 9.4% (6/64) patients with CHD. From 18 patients referred because of the hypocalcaemia, six (33.3%) had 22q11.2 deletion. In the group of 31 children with dysmorphic traits, the diagnosis was confirmed in two (6.4%) patients. None of the 58 children with palatal anomalies showed evidence of 22q11.2 deletion. Conclusions: Testing for the 22q11.2 microdeletion can be recommended in all patients with conotruncal heart defects and in patients with hypocalcaemia. It should be also considered in patients presenting only with dysmorphic traits suggestive of del 22q11.2, while screening in patients with cleft palate is not warranted