Familial History in Ovarian Teratomas Is a Frequent Event: 22 Years' Experience at a Single Center.

Background: Ovarian mature teratoma represents the most common benign neoplasm among pediatric germ cell tumors. This study reports the prevalence and characteristics of familial forms identified in a single center over 22 years in order to better understand possible familial predispositions to ovarian teratoma.

Methods: The records of all patients who were surgically treated for ovarian teratoma between 2000 and 2022 were retrospectively reviewed.

Aarskog-Scott syndrome: a clinical study based on a large series of 111 male patients with a pathogenic variant in and management recommendations.

Background: Aarskog-Scott syndrome (AAS) is a rare condition with multiple congenital anomalies, caused by hemizygote variants in the gene. Its description was based mostly on old case reports, in whom a molecular diagnosis was not always available, or on small series. The aim of this study was to better delineate the phenotype and the natural history of AAS and to provide clues for the diagnosis and the management of the patients.

CIROZ is dispensable in ancestral vertebrates but essential for left-right patterning in humans.

Four genes-DAND5, PKD1L1, MMP21, and CIROP-form a genetic module that has specifically evolved in vertebrate species that harbor motile cilia in their left-right organizer (LRO). We find here that CIROZ (previously known as C1orf127) is also specifically expressed in the LRO of mice, frogs, and fish, where it encodes a protein with a signal peptide followed by 3 zona pellucida N domains, consistent with extracellular localization. We report 16 individuals from 10 families with bi-allelic CIROZ inactivation variants, which cause heterotaxy with congenital heart defects.

Next Generation Phenotyping and Synthetic Faces in Coffin Siris Syndrome.

Diagnostic wandering and delayed management are major issues in rare diseases. Here, we report a new Next-Generation Phenotyping (NGP) model for diagnosing Coffin Siris syndrome (CSS) on clinical photographs among controls and distinguish the different genotypes. This retrospective and prospective study, conducted from 1998 to 2023, included frontal and lateral pictures of confirmed CSS.

The characterization of new de novo CACNA1G variants affecting the intracellular gate of Cav3.1 channel broadens the spectrum of neurodevelopmental phenotypes in SCA42ND.

Purpose: Missense de novo variants in CACNA1G, which encodes the Cav3.1 T-type calcium channel, have been associated with a severe, early-onset form of cerebellar disorder with neurodevelopmental deficits (SCA42ND). We explored a large series of pediatric cases carrying heterozygous variants in CACNA1G to further characterize genotype-phenotype correlations in SCA42ND.

GPATCH11 variants cause mis-splicing and early-onset retinal dystrophy with neurological impairment.

Here we conduct a study involving 12 individuals with retinal dystrophy, neurological impairment, and skeletal abnormalities, with special focus on GPATCH11, a lesser-known G-patch domain-containing protein, regulator of RNA metabolism. To elucidate its role, we study fibroblasts from unaffected individuals and patients carrying the recurring c.328+1 G > T mutation, which specifically removes the main part of the G-patch domain while preserving the other domains.

Equity and justice in medical education: mapping a longitudinal curriculum across 4 years.

Background: In 2024 in the United States there is an attack on diversity, equity, and inclusion initiatives within education. Politics notwithstanding, medical school curricula that are current and structured to train the next generation of physicians to adhere to our profession's highest values of fairness, humanity, and scientific excellence are of utmost importance to health care quality and innovation worldwide. Whereas the number of anti-racism, diversity, equity, and inclusion (ARDEI) curricular innovations have increased, there is a dearth of published longitudinal health equity curriculum models.

Chromatin assembly factor subunit CHAF1A as a monogenic cause for oculo-auriculo-vertebral spectrum.

Oculo-auriculo-vertebral spectrum (OAVS) is characterized by abnormal development of the 1st and 2nd branchial arches. Despite arguments against a monogenic condition, a few genes have been involved in a minority of cases. We now report heterozygous, presumably loss-of function variants in the CHAF1A gene in 8 individuals, including 3 members of the same family.

Identification of a DNA methylation episignature for recurrent constellations of embryonic malformations.

The term "recurrent constellations of embryonic malformations" (RCEM) is used to describe a number of multiple malformation associations that affect three or more body structures. The causes of these disorders are currently unknown, and no diagnostic marker has been identified. Consequently, providing a definitive diagnosis in suspected individuals is challenging.

Statement of Partnership and Humility: A Structural Intervention to Improve Equity and Justice in Medical Education.

Problem: Due to generational exposure to the Black Lives Matter movement, other antibias social movements, and diverse peer advocacy groups, health professions students are often more knowledgeable than their teachers about ways in which systemic racism and bias have led to scientific inaccuracies that contribute to health inequities. However, traditional hierarchies and concerns about retaliation may limit educational communities from benefiting maximally from students' contributions.

Approach: In spring 2021, faculty and students at the Vagelos College of Physicians and Surgeons, Columbia University, designed a structural innovation to engage faculty and students in partnership toward decreasing bias in medical education.

TREX tetramer disruption alters RNA processing necessary for corticogenesis in THOC6 Intellectual Disability Syndrome.

THOC6 variants are the genetic basis of autosomal recessive THOC6 Intellectual Disability Syndrome (TIDS). THOC6 is critical for mammalian Transcription Export complex (TREX) tetramer formation, which is composed of four six-subunit THO monomers. The TREX tetramer facilitates mammalian RNA processing, in addition to the nuclear mRNA export functions of the TREX dimer conserved through yeast.

The Promise and Perils of Artificial Intelligence in Health Professions Education Practice and Scholarship.

Artificial intelligence (AI) methods, especially machine learning and natural language processing, are increasingly affecting health professions education (HPE), including the medical school application and selection processes, assessment, and scholarship production. The rise of large language models over the past 18 months, such as ChatGPT, has raised questions about how best to incorporate these methods into HPE. The lack of training in AI among most HPE faculty and scholars poses an important challenge in facilitating such discussions.

Differential alternative splicing analysis links variation in ZRSR2 to a novel type of oral-facial-digital syndrome.

Purpose: Oral-facial-digital (OFD) syndromes are genetically heterogeneous developmental disorders, caused by pathogenic variants in genes involved in primary cilia formation and function. We identified a previously undescribed type of OFD with brain anomalies, ranging from alobar holoprosencephaly to pituitary anomalies, in 6 unrelated families.

Methods: Exome sequencing of affected probands was supplemented with alternative splicing analysis in patient and control lymphoblastoid and fibroblast cell lines, and primary cilia structure analysis in patient fibroblasts.

Bi-allelic loss-of-function variants in WBP4, encoding a spliceosome protein, result in a variable neurodevelopmental syndrome.

Over two dozen spliceosome proteins are involved in human diseases, also referred to as spliceosomopathies. WW domain-binding protein 4 (WBP4) is part of the early spliceosomal complex and has not been previously associated with human pathologies in the Online Mendelian Inheritance in Man (OMIM) database. Through GeneMatcher, we identified ten individuals from eight families with a severe neurodevelopmental syndrome featuring variable manifestations.

Clinico-biological refinement of BCL11B-related disorder and identification of an episignature: A series of 20 unreported individuals.

Purpose: BCL11B-related disorder (BCL11B-RD) arises from rare genetic variants within the BCL11B gene, resulting in a distinctive clinical spectrum encompassing syndromic neurodevelopmental disorder, with or without intellectual disability, associated with facial features and impaired immune function. This study presents an in-depth clinico-biological analysis of 20 newly reported individuals with BCL11B-RD, coupled with a characterization of genome-wide DNA methylation patterns of this genetic condition.

Methods: Through an international collaboration, clinical and molecular data from 20 individuals were systematically gathered, and a comparative analysis was conducted between this series and existing literature.