Prenatal diagnosis of bilateral anophthalmia: Identifying de novo SOX2 variant.

A 26 year old nulligravida presented at 24 weeks gestation for the second opinion of abnormal fetal profile and mid-face views on ultrasound at another institution. A detailed fetal anatomic ultrasound at our facility revealed the absence of fetal lens and globes bilaterally consistent with bilateral anophthalmia (HP: 0000528) without other anomalies. Karyotype and chromosomal microarray analysis were completed from amniocentesis sample. After these results, duo exome testing with paternal sequencing was completed from proband amniotic fluid sample and parental blood samples. A pathogenic variant in SOX2 (NM_003106.3: c.513C>G p.(Tyr171*Ter)) with heterozygous autosomal dominant inheritance resulted. On duo exome testing with paternal segregation analysis, the variant was found to be consistent with likely sporadic de novo inheritance. The SOX2 variant reported is consistent with the fetal phenotype in this case. While germline mosaicism could exist, this identified variant provided the family with a likely explanation for this proband's finding. This ultrasound and genetic testing allowed the family to make decisions related to planning in current and future pregnancies.

Obstetric-Focused POCUS Training for Medical Students.

Point of care ultrasound (POCUS) is rapidly expanding throughout the United States. Due to its ability to quickly and accurately diagnose and guide therapy for critical conditions, POCUS is becoming routine in many specialties, with established guidelines in fields such as emergency medicine and critical care 1, 2, 3. For example, a study entitled "Ultrasound Integration in Undergraduate Medical Education: Comparison of Ultrasound Proficiency Between Trained and Untrained Medical Students" initiated an Emergency Medicine POCUS curriculum for first-year medical students that showed an increase in ultrasound capability 4. In short, as POCUS becomes more common practice, medical schools are beginning to implement POCUS training into their undergraduate medical education; studies from these institutions demonstrate that implementing a formal ultrasound curriculum into preclinical medical education significantly increases medical students' POCUS capabilities4, 5 and assisted in their understanding and learning of anatomy 6, 7.

ChatGPT: a pioneering approach to complex prenatal differential diagnosis.

This commentary examines how ChatGPT can assist healthcare teams in the prenatal diagnosis of rare and complex cases by creating a differential diagnoses based on deidentified clinical findings, while also acknowledging its limitations.

COL10A1 expression is elevated in diverse solid tumor types and is associated with tumor vasculature.

AIM: The identification of molecular markers that are upregulated in multiple tumor types could lead to novel diagnostic and therapeutic strategies. The authors screened a panel of RNAs prepared from diverse tumors and tumor cell lines, and compared them with normal tissues and cultured somatic cell types, in order to identify candidate genes expressed in a broad spectrum of tumor types. MATERIALS & METHODS: Gene expression microarray analysis was carried out on 128 individual tumor samples representing over 20 tumor types, 85 samples representing 31 diverse normal tissue types, 68 tumor cell lines and 97 diverse normal primary cell cultures. Genes were ranked for elevated expression across a large number and variety of tumors relative to normal tissues. RESULTS & CONCLUSION: COL10A1 was identified as a gene with restricted expression in most normal tissues and elevated expression in many diverse tumor types. By contrast, COL10A1 expression was undetectable in the 68 tumor cell lines surveyed in this study. Immunofluorescence studies localized collagen, type X, α-1 (collagen X) staining to tumor vasculature in breast tumors, whereas the vasculature of normal breast tissue was either collagen X-negative or had markedly lower levels. The tumor microenvironment-specific expression of collagen X, together with its localization in the vasculature, may facilitate its use as a novel target for the diagnosis and treatment of diverse solid tumor types.

Human embryonic stem cell-derived neural crest cells capable of expressing markers of osteochondral or meningeal-choroid plexus differentiation.

AIMS: The transcriptome and fate potential of three diverse human embryonic stem cell-derived clonal embryonic progenitor cell lines with markers of cephalic neural crest are compared when differentiated in the presence of combinations of TGFß3, BMP4, SCF and HyStem-C matrices. MATERIALS & METHODS: The cell lines E69 and T42 were compared with MEL2, using gene expression microarrays, immunocytochemistry and ELISA. RESULTS: In the undifferentiated progenitor state, each line displayed unique markers of cranial neural crest including TFAP2A and CD24; however, none expressed distal HOX genes including HOXA2 or HOXB2, or the mesenchymal stem cell marker CD74. The lines also showed diverse responses when differentiated in the presence of exogenous BMP4, BMP4 and TGFß3, SCF, and SCF and TGFß3. The clones E69 and T42 showed a profound capacity for expression of endochondral ossification markers when differentiated in the presence of BMP4 and TGFß3, choroid plexus markers in the presence of BMP4 alone, and leptomeningeal markers when differentiated in SCF without TGFß3. CONCLUSION: The clones E69 and T42 may represent a scalable source of primitive cranial neural crest cells useful in the study of cranial embryology, and potentially cell-based therapy.

Elevated expression of cancer/testis antigen FSIP1 in ER-positive breast tumors.

AIM: The study aimed to identify and characterize highly specific breast tumor biomarkers. METHODS: A microarray data set comprised of 513 diverse normal and tumor mRNA samples was analyzed to identify breast tumor biomarkers with minimal expression in normal tissues. RESULTS: FSIP1 was identified as a breast tumor biomarker with elevated mRNA expression in breast tumors and minimal expression in most normal tissues except the testis. Quantitative real-time PCR confirmed the elevated expression of FSIP1 mRNA in breast tumors and revealed a significant correlation with ER-positive status. Immunofluorescence staining of breast tumor sections showed that the majority of breast tumors examined in this study (20 out of 22) expressed detectable FSIP1 protein, with significantly higher than average expression in ER-positive versus ER-negative breast tumors. CONCLUSION: The prevalence and uniformity of FSIP1 expression in breast tumors, taken together with the highly restricted expression in normal tissues, suggests that FSIP1 may be an attractive target for breast cancer immunotherapy.

Seven diverse human embryonic stem cell-derived chondrogenic clonal embryonic progenitor cell lines display site-specific cell fates.

AIM: The transcriptomes of seven diverse clonal human embryonic progenitor cell lines with chondrogenic potential were compared with that of bone marrow-derived mesenchymal stem cells (MSCs). MATERIALS & METHODS: The cell lines 4D20.8, 7PEND24, 7SMOO32, E15, MEL2, SK11 and SM30 were compared with MSCs using immunohistochemical methods, gene expression microarrays and quantitative real-time PCR. RESULTS: In the undifferentiated progenitor state, each line displayed unique combinations of site-specific markers, including AJAP1, ALDH1A2, BMP5, BARX1, HAND2, HOXB2, LHX1, LHX8, PITX1, TBX15 and ZIC2, but none of the lines expressed the MSC marker CD74. The lines showed diverse responses when differentiated in the presence of combinations of TGF-ß3, BMP2, 4, 6 and 7 and GDF5, with the lines 4D20.8, SK11, SM30 and MEL2 showing osteogenic markers in some differentiation conditions. The line 7PEND24 showed evidence of regenerating articular cartilage and, in some conditions, markers of tendon differentiation. CONCLUSION: The scalability of site-specific clonal human embryonic stem cell-derived embryonic progenitor cell lines may provide novel models for the study of differentiation and methods for preparing purified and identified cells types for use in therapy.