Birth outcomes of cases with different congenital heart defects - a population-based study

Background: In general, previous epidemiological studies evaluated congenital heart defects (CHDs) together. The aim of the present study was to identify possible etiological factors of different CHD-entities, because the underlying causes are unclear in the vast majority of patients.Objectives: Different CHD-entities as homogeneously as possible with confirmed diagnoses were analyzed in the population-based large dataset of the Hungarian Case-Control Surveillance of Congenital Abnormalities.Methods: 3,750 live-born singleton CHD-patients were analyzed according to birth outcomes, i.e. gestational age at delivery and birth weight, the rate of preterm birth, low birthweight and small for gestational age.Results: The major findings of the study showed that cases with different CHD-entities had shorter gestational age at delivery and lower mean birth weight, and these variables associated with a higher rate of preterm birth and particularly with a much higher rate of low birthweight and small for gestational age. This study showed the importance of sex in the birth outcomes of some CHD-entities. The question is why several CHD-entities manifested more frequently in newborns with intrauterine growth restriction because fetal heart has a passive role before birth without pulmonary circulation.Conclusions: The birth outcomes of cases indicate the effect of CHDs for fetal development. In addition maternal confounders have to consider. Finally, CHDs and intrauterine growth restriction as two developmental errors may have a common route, thus fetal growth and birthweight associated gene polymorphisms may have a role in the origin of CHDs.</jats:p

Egészséges gyermek születése karyomapping eljárással történő preimplantációs genetikai diagnózist követően | Unaffected child born following preimplantation genetic diagnosis with karyomapping

Absztrakt: Az asszisztált reprodukciós beavatkozáshoz kötötten elvégzett preimplantációs genetikai diagnózis mára már egy elterjedt, befogadott módszer szerte a világon. A karyomapping egy teljes genom haplotipizálásán alapuló módszer, ami egypontos nukleotid polimorfizmus array segítségével képes monogénes megbetegedéseket diagnosztizálni. Célunk a karyomapping mint embriódiagnosztikai módszer bevezetése klinikánkon. Primer örökletes glaucomával született gyermek szülei jelentkeztek klinikánkon preimplantációs genetikai diagnózis eljárással kombinált in vitro fertilizációs kezelésre. Hat leszívott petesejtből a három érett petesejt került megtermékenyítésre. A normális termékenyülés jeleit egy zigóta mutatta, amit öt napig tenyésztettünk. Az ötödik napon embrióbiopsziát végeztünk, és a mintát karyomapping eljárással értékeltük. Az embriót heterozigóta hordozóként diagnosztizáltuk. Fagyasztott embriótranszfer eredményeképpen a terhesség 39. hetében egészséges lánygyermek született. A karyomapping eljárást mint preimplantációs genetikai diagnózis módszert Magyarországon klinikánkon elsőként alkalmaztuk sikeresen. A módszer bonyolult preklinikai előkészítés nélkül nagy megbízhatósággal alkalmas monogénes megbetegedést okozó mutációk diagnosztizálására. Orv. Hetil., 2016, 157(51), 2048–2050. | Abstract: Preimplantation genetic diagnosis for single gene defects is a well established method in assisted reproductive technologies. Karyomapping is a genome wide parental haplotyping using a high density single nucleotide polymorphism array that allows the diagnosis of any single gene defects. A couple with an affected child with primary congenital glaucoma attended at our clinic. Six oocyte-cumulus-complex was retrieved and all three mature oocytes were inseminated. One zygote showed the signs of normal fertilization and was cultured for five days. Trophectoderm biopsy and karyomapping analysis were carried out. Result showed a heterozygous carrier for primary congenital glaucoma. Embryo was thawed and transferred and a healthy girl was delivered at term. Here we report the first live birth following in vitro fertilization combined with preimplantation genetic diagnosis using karyomapping in Hungary. Karyomapping is able to accurately detect single gene disorders from a limited amount of samples without a significant preclinical workup. Orv. Hetil., 2016, 157(51), 2048–2050

Endometrial polyps in infertility patients: The first study of their clinical characteristics

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Currently favored sampling practices for tumor sequencing can produce optimal results in the clinical setting

Tumor heterogeneity is a consequence of clonal evolution, resulting in a fractal-like architecture with spatially separated main clones, sub-clones and single-cells. As sequencing an entire tumor is not feasible, we ask the question whether there is an optimal clinical sampling strategy that can handle heterogeneity and hypermutations? Here, we tested the effect of sample size, pooling strategy as well as sequencing depth using whole-exome sequencing of ovarian tumor specimens paired with normal blood samples. Our study has an emphasis on clinical application—hence we compared single biopsy, combined local biopsies and combined multi-regional biopsies. Our results show that sequencing from spatially neighboring regions show similar genetic compositions, with few private mutations. Pooling samples from multiple distinct regions of the primary tumor did not increase the overall number of identified mutations but may increase the robustness of detecting clonal mutations. Hypermutating tumors are a special case, since increasing sample size can easily dilute sub-clonal private mutations below detection thresholds. In summary, we compared the effects of sampling strategies (single biopsy, multiple local samples, pooled global sample) on mutation detection by next generation sequencing. In view of the limitations of present tools and technologies, only one sequencing run per sample combined with high coverage (100–300 ×) sequencing is affordable and practical, regardless of the number of samples taken from the same patient. © 2020, The Author(s)