All Publications

  • A Complex Case of Langer-Giedion Syndrome, Cornelia de Lange Syndrome Type 4, and Hereditary Multiple Osteochondromas with Mosaic 8q23.1-q24.12 Deletion. Genes Valientes, S. D., Wang, H. 2026; 17 (2)

    Abstract

    Langer-Giedion syndrome (LGS), also known as trichorhinophalangeal syndrome type II (TRPS II; OMIM #150230), is a contiguous-gene deletion disorder caused by haploinsufficiency of TRPS1 and EXT1. Cornelia de Lange syndrome (CdLS) is genetically heterogeneous; heterozygous variants in RAD21 cause the milder CdLS type 4 phenotype (OMIM #614701). Because RAD21 lies between TRPS1 and EXT1, overlapping phenotypes may arise when all three genes are deleted. We report a unique case of a 4-year-old female presenting with a blended phenotype of Langer-Giedion Syndrome (LGS) and Cornelia de Lange Syndrome (CdLS) type 4. This case is distinct from previously reported 8q deletions in three key aspects: (1) Complex Genomic Architecture: Chromosomal microarray revealed a novel complex rearrangement consisting of a 13.01 Mb mosaic interstitial deletion at 8q23.1-q24.12, flanked by two large duplications (21.5 Mb at 8q11.23-q23.1 and 25.78 Mb at 8q24.12-q24.3). (2) Rare Mosaicism: This represents only the second reported case of mosaicism affecting this contiguous gene region. Notably, the patient demonstrates a "mosaic rescue" effect, where the mosaicism appears to have mitigated the neurodevelopmental phenotype (the patient is bilingual and ambulatory) while failing to protect the skeleton. (3) First Bone-Specific Therapy: The patient suffered from severe, recurrent fractures due to a synergistic "double hit" of TRPS1-related osteopenia and EXT1-related exostoses. We report the first successful use of bisphosphonate therapy (pamidronate) in this specific mosaic profile, which resulted in a complete cessation of fractures during a 12-month follow-up. This case underscores the utility of detailed microarray analysis in complex phenotypes and suggests bisphosphonates as a viable rescue therapy for refractory syndromic osteoporosis.

    View details for DOI 10.3390/genes17020175

    View details for PubMedID 41751561

  • Updates in Trisomy 18. NeoReviews Srinivasan, K., Canarte, C., Valientes, S. D., Sanchez-Lara, P. A., Langston, S. J. 2025; 26 (12): e820-e834

    Abstract

    Aneuploidies represent some of the most common genetic abnormalities within the pediatric population. Among them, trisomies 13, 18, and 21 constitute the most prevalent syndromes. Unlike trisomy 21, trisomies 13 and 18 have historically been regarded as having significant morbidity and mortality leading to being labeled "lethal" conditions. However, within the last few decades there is a growing body of evidence that the long-term outcomes of newborns specifically affected by trisomy 18 are exceeding these preconceived, historical notions. This shift results from increased postnatal intervention due to shared decision-making with families and medical teams. This review summarizes the clinical manifestations of trisomy 18 syndrome but also explores the updated long-term outcomes and subsequent guidance for future medical surveillance in a population of newborns previously expected to die before their first birthday.

    View details for DOI 10.1542/neo.26-12-082

    View details for PubMedID 41319979

  • Early-life exercise primes the murine neural epigenome to facilitate gene expression and hippocampal memory consolidation. Communications biology Raus, A. M., Fuller, T. D., Nelson, N. E., Valientes, D. A., Bayat, A., Ivy, A. S. 2023; 6 (1): 18

    Abstract

    Aerobic exercise is well known to promote neuroplasticity and hippocampal memory. In the developing brain, early-life exercise (ELE) can lead to persistent improvements in hippocampal function, yet molecular mechanisms underlying this phenomenon have not been fully explored. In this study, transgenic mice harboring the "NuTRAP" (Nuclear tagging and Translating Ribosome Affinity Purification) cassette in Emx1 expressing neurons ("Emx1-NuTRAP" mice) undergo ELE during adolescence. We then simultaneously isolate and sequence translating mRNA and nuclear chromatin from single hippocampal homogenates containing Emx1-expressing neurons. This approach allowed us to couple translatomic with epigenomic sequencing data to evaluate the influence of histone modifications H4K8ac and H3K27me3 on translating mRNA after ELE. A subset of ELE mice underwent a hippocampal learning task to determine the gene expression and epigenetic underpinnings of ELE's contribution to improved hippocampal memory performance. From this experiment, we discover gene expression - histone modification relationships that may play a critical role in facilitated memory after ELE. Our data reveal candidate gene-histone modification interactions and implicate gene regulatory pathways involved in ELE's impact on hippocampal memory.

    View details for DOI 10.1038/s42003-022-04393-7

    View details for PubMedID 36611093

    View details for PubMedCentralID PMC9825372

  • An Improved Method for Individual Tracking of Voluntary Wheel Running in Pair-housed Juvenile Mice. Bio-protocol Valientes, D. A., Raus, A. M., Ivy, A. S. 2021; 11 (13): e4071

    Abstract

    Rodent cages equipped with access to a voluntary running wheel are commonly used to study the effects of aerobic physical activity on physiology and behavior. Notable discoveries in exercise neurobiology, including the key role of brain-derived neurotrophic factor (BDNF) in neural plasticity and cognition, have been made using rodents housed with voluntary running wheels. A major advantage of using home-cage running wheels over treadmills is the elimination of stress potentially associated with forced running. In addition, voluntary wheel running may simulate a more natural running pattern in laboratory mice. Singly housing mice with voluntary running wheels is traditionally employed to obtain exact quantitation of the distance ran; however, social isolation stress is often ignored to obtain precise running distances. Moreover, voluntary exercise studies in adolescent mice must consider the neurodevelopmental implications of isolation stress. In this protocol, we wean 21-day-old mouse pups directly into running wheel-equipped cages and pair-house them to reduce the impact of social isolation and other developmentally specific factors that could adversely affect their behavior or development. Individual running distances are obtained from each mouse in the cage using a radio-frequency identification (RFID) ear tag and a hidden antenna placed directly under the running wheel. We have demonstrated that voluntary running during a specific juvenile-adolescent developmental period can improve hippocampal memory when tested during adolescence ( Ivy et al., 2020 ). Individual exercise tracking of group-housed mice can enable future studies to precisely correlate the amount of exercise with readouts such as cell-specific gene expression, epigenetic mechanisms, serum biomarkers, and behavior, in an intra-individual manner. Graphic abstract: Figure 1.Illustration of the dual RFID and Vital View system for individual mouse running in a pair-housed cage.

    View details for DOI 10.21769/BioProtoc.4071

    View details for PubMedID 34327268

    View details for PubMedCentralID PMC8292121