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Bosch–Boonstra–Schaaf optic atrophy syndrome (BBSOAS) is an autosomal dominant disease characterized by developmental delay, intellectual disability, and optic atrophy with a variable expression of other clinical features (dysmorphic features, autistic behaviour, corpus callosum hypoplasia and seizures). To date, approximately a hundred cases of the syndrome have been described, with an estimated prevalence of 1 in 100 000–250 000. BBSOAS is caused by the loss of function of the NR2F1 gene (nuclear receptor subfamily 2 group F member 1), which encodes the COUP‐TFI (Chicken ovalbumin upstream promotor‐transcription factor 1). COUP‐TFI functions as a homodimer and is one of the major transcriptional regulators directing cortical arealization, cell differentiation and maturation. Most cases of BBSOAS occur de novo, and one case was previously described in which the disease resulted from gonadal mosaicism. In the present case, we report two sisters with BBSOAS, a novel nonsense mutation in the NR2F1 gene and potential gonadal mosaicism as the cause of this rare disease, making it the second such case described in the literature. [ABSTRACT FROM AUTHOR]

Background Objectives Search strategy Selection criteria Data collection and analysis Results Conclusions Despite various genomic approaches used in prior studies investigating the association of maternal genetic variability with spontaneous preterm birth (sPTB), results show inconsistency and contradictions.To conduct a systematic review of studies analyzing the association between maternal genetic variants and sPTB, evaluate retrieved studies based on selection criteria, classify studies into hypothesis‐based and hypothesis‐free, and perform a meta‐analysis to identify the strongest associations.PubMed, Scopus, and reference lists were searched until October 2024.English‐language, case–control, cross‐sectional, and prospective cohort studies examining the association between maternal genetic variations and sPTB were included.Data on authors, publication year, ethnicity, genes/variants, P values, study type, sample size, inclusion criteria, and methods were collected. The association strength was estimated using odds ratios with 95% confidence intervals.Eighty‐one studies met eligibility criteria: 73 utilized a hypothesis‐based and 14 a hypothesis‐free approach. Thirty‐five studies qualified for a meta‐analysis, revealing a significant association in tumor necrosis factor α (rs1800629) gene for alleles and additive and recessive genetic models (P ≤ 0.05). From the hypothesis‐free approach, 13 genes reached global significance in association with sPTB (P < 5 × 10−8).No single gene or variant was consistently associated with sPTB risk among studies. Hypothesis‐based analyses highlighted tumor necrosis factor α (rs1800629) as a modest signal, while hypothesis‐free approaches identified 13 genes with genome‐wide significance, pointing to new research directions in understanding sPTB genetics. [ABSTRACT FROM AUTHOR]

Problem Aberrant DNA methylation has been suggested as a potential cause of recurrent spontaneous abortion ( RSA). Considering the growing evidence on the important roles of DNA methylation in gametogenesis and early pregnancy, we investigated the potential association of DNA methyltransferase gene polymorphisms ( DNMT1 rs2228611, DNMT3A rs1550117, DNMT3B rs1569686) with RSA in Slovenian reproductive couples. Method of study A total of 146 couples with ≥3 consecutive spontaneous abortions and 149 control women and men with ≥2 normal pregnancies were included. Genotyping was performed using PCR- RFLP methods. Results We found a statistically significant higher frequency of the DNMT3B rs1569686 GG genotype (X2=7.37; P = .025) and G allele (X2 = 6.33; P = .012) in RSA women compared with controls. Moreover, the odds for RSA in women were increased under the recessive genetic model ( GGvs TG+ TT: OR=1.92; 95% CI=1.18-3.09; P = .008). Conclusion DNMT3B rs1569686 gene polymorphism in women might be a genetic marker for the susceptibility to RSA. [ABSTRACT FROM AUTHOR]

Langer-Giedion syndrome (LGS) is a contiguous gene syndrome caused by a hemizygous deletion on chromosome 8q23.3-q24.11 involving TRPS1 and EXT1 genes. We report on a girl with LGS phenotype and a 7.5 Mb interstitial deletion at chromosome 8q23.3-q24.13. Array-comparative genomic hybridization (a-CGH) revealed a deletion encompassing only the EXT1 and not the TRPS1 gene. Even though the deletion of TRPS1 and EXT1 genes is responsible for craniofacial and skeletal features of LGS, there have been previous reports of patients with LGS phenotype and 8q24 deletions leaving the TRPS1 gene intact. To our knowledge, this is the third such case. Our patient differs from previously reported LGS patients without TRPS1 gene deletion in that she has the typical LGS facial dysmorphism and skeletal abnormalities. However, the girl is of normal height and has only a mild developmental delay. Additionally, she has dyslalia and premature adrenarche classified as Tanner stage 3 premature pubarche which have not yet been described as features of LGS. We examine the molecular breakpoints and phenotypes of our patient and previously reported cases. © 2012 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Problem Recurrent spontaneous abortion (RSA) is a common clinical problem with a complex etiology of genetic and non-genetic causes, which remains to be fully determined. IGF-2 stimulates trophoblast invasion, proliferation and maturation of placenta, while H19 RNA suppresses growth. As genomic imprinting plays a critical role in the development of placenta and embryo, our aim was to evaluate the possible role of variations in IGF-2 and H19 imprinted genes as factors of predisposition for RSA. Method of study A case–control study was conducted to determine the association between IGF-2 and H19 gene polymorphisms and the susceptibility to RSA in 113 couples with RSA and 226 controls. PCR/RFLP were performed to analyze IGF-2 ApaI and H19 HhaI polymorphisms. Results We found a statistically significant difference in the genotype frequency distribution of IGF-2 ApaI polymorphism between males from couples with RSA and healthy males (χ 2(2) = 45.12; P < 0.0001). There were no differences in the genotype and allele distribution of H19 polymorphism frequencies, or for the IGF-2 ApaI polymorphism between female groups. Conclusion The presence of IGF-2 ApaI polymorphism in partners of RSA women could affect IGF-2 level of expression in placenta and embryo and represent a risk factor for RSA susceptibility. [ABSTRACT FROM AUTHOR]

Background: Our aim was to conduct a comprehensive genetic evaluation using the combination of QF‐PCR (quantitative fluorescence polymerase chain reaction) and aCGH (array comparative genomic hybridization) for the detection of the frequency and type of chromosome aberrations in recurrent miscarriage (RM) in the clinical setting. Methods: This retrospective study was conducted on 73 first‐trimester products of conception (POC) between September 2014 and February 2017. The POCs were collected from 73 women with at least one previous miscarriage and analyzed for chromosomal anomalies using QF‐PCR and aCGH as part of the routine clinical evaluation. Results: Chromosome aberrations were detected in 52/73 POCs (71.2%), of which 41 (56.2%) were identified by QF‐PCR and an additional 11 (15.1%) by aCGH. Numerical aberrations constituted 92.3% of abnormalities, with trisomies as the most common subtype (72.9%). Causative structural aberrations were found in three samples (5.8%). The frequency of chromosome aberrations was not dependent on the number of previous miscarriages, whereas it significantly increased with advanced maternal age. Conclusion: Our results confirm that chromosome aberrations are the most common cause of RM and that QF‐PCR and aCGH combination should be included in the routine genetic analysis of POCs of couples with miscarriage. [ABSTRACT FROM AUTHOR]

In the March issue of the Journal in 2012, we reported on a girl with Langer-Giedion syndrome (LGS) phenotype and a 7.5 Mb interstitial deletion at 8q23.3q24.13, encompassing the EXT1, but not the TRPS1 gene. Recent discoveries have shown that heterozygous intragenic mutations or contiguous gene deletions including the RAD21 gene, which is located downstream of the TRPS1 gene, are the cause of Cornelia de Lange syndrome-4. Considering that the interstitial deletion in our patient included the RAD21 and 30 other RefSeq genes, we would like to suggest a revision of the diagnosis reported in our previous paper and compare our patient to other reported patients with Cornelia de Lange syndrome-4 caused by heterozygous deletions of chromosome 8q24. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]