Next generation sequencing (NGS) is a rapidly developing area in genetics. Utilizing this technology in the management of disorders with complex genetic background and not recurrent mutation hot spots can be extremely useful. In this study, we applied NGS, namely semiconductor sequencing to determine the most significant osteogenesis imperfecta-related genetic variants in the clinical practice. We selected genes coding collagen type I alpha-1 and-2 (COL1A1, COL1A2) which are responsible for more than 90% of all cases. CRTAP and LEPRE1/P3H1 genes involved in the background of the recessive forms with relatively high frequency (type VII and VIII) represent less than 10% of the disease. In our six patients (1–41 years), we identified 23 different variants. We found a total of 14 single nucleotide variants (SNV) in COL1A1 and COL1A2, 5 in CRTAP and 4 in LEPRE1. Two novel and two already well-established pathogenic SNVs have been identified. Among the newly recognized mutations, one results in an amino acid change and one of them is a stop codon. We have shown that a new full-scale cost-effective NGS method can be developed and utilized to supplement diagnostic process of osteogenesis imperfecta with molecular genetic data in clinical practice.
Sensitivity of leukemic blasts to steroid therapy is one of the prognostic factors in acute lymphoblastic leukemia (ALL) in children. We examined the number of steroid receptors and the increase in the apoptotic index in peripheral blast cells after administration of prednisolone monotherapy in 21 children with ALL. A new diagnostic method was established based on determination of the apoptotic index in peripheral blood lymphoblasts to evaluate the steroid sensitivity of leukemic cells during the first day of therapy. The increase in apoptotic ratio, analyzed by morphologic and/or flow cytometric studies, was most expressed in the first 6 hours of treatment. The apoptotic ratio showed a good correlation with the clinical response. The number of steroid receptors (gcRs) on the blast cells was also examined, but it proved to be less informative than the in vivo steroid response itself.
We report the association of Beckwith-Wiedemann syndrome (BWS) and a residual acid sphingomyelinase (ASM) activity of about 35% in a 23 months old Hungarian boy. Besides the classical triad of exomphalos, macroglossia and gigantism some other BWS-related features: polyhydramnios (known from the praenatal history), hemihypertrophy, craniofacial dysmorphy, a mild mental retardation, bilaterally undescended testes, cardiac anomalies and a terminally developed, fatal embryonal rhabdomyosarcoma were present in the patient. The decreased activity of the ASM was measured in the patient s skin fibroblasts. This result, with hepatomegaly, mental retardation, feeding problems, a failure to thrive and muscle-hypotony, partially resembled the ASM-deficient forms of Niemann-Pick disease (NPD). Morphological analysis of the bone-marrow cells gave normal results. There was no chromosomal alteration found by conventional karyotyping of the patient s lymphocytes.BWS-associated genes as well as the human ASM gene (SMPD1) are all located at 11p15. DNA-studies by region specific markers as well as mutational analysis for the most common NPD-mutations are planned in the future. This is the first report on the simultaneous occurrence of BWS and ASM-deficiency.
A genetikai diagnosztikai és szűrővizsgálatok számának gyors növekedése a genetikai tanácsadás gyakorlatának és szabályozásának újragondolását kívánja. A keletkező hatalmas adatmennyiség tárolásával, küldésével kapcsolatos biztonsági szempontok részletes szabályozását is szükségessé teszi. A genetika az egészségügy gyorsan fejlődő területe, komplexitása a közeli jövőben a mesterséges intelligencia segítségét igényli.
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