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.