Study of the Pathophysiology of RNU4ATAC and RTTN Associated Syndromes: Microcephalic Osteodysplastic Primordial Dwarfism Types I and III, Roifman and Lowry-Wood Syndromes

What this Trial Is About

Researchers are investigating rare developmental disorders linked to mutations in the RNU4ATAC and RTTN genes. These disorders include Taybi-Linder Syndrome, Roifman Syndrome, Lowry-Wood Syndrome, and Microcephalic Osteodysplastic Primordial Dwarfism Types I and III. These conditions cause growth delays before and after birth, small head size, skeletal problems, intellectual disability, retinal issues, and immune system deficiencies. The study aims to understand how defects in minor RNA splicing caused by these gene mutations affect cell functions and contribute to these syndromes. The study involves collecting biological samples such as blood and skin biopsies from patients with bi-allelic mutations in RNU4ATAC or RTTN, their parents with mono-allelic mutations, and fetuses with these mutations after miscarriage or medical abortion. These samples will help create induced pluripotent stem cell lines and analyze gene expression, RNA splicing, cell functions, and tissue structure. The study does not involve drug treatments but focuses on laboratory and cellular analyses. Participants will provide blood and possibly skin samples, while parents of fetuses with mutations may consent to tissue biopsies after pregnancy termination. Researchers will study the cellular consequences of RNU4ATAC mutations over five years, including minor splicing anomalies and neuronal differentiation issues. The research includes transcriptomic, biochemical, and cellular assessments to better understand the diseases' mechanisms and does not involve randomization or blinding.

Study of the Pathophysiology of RNU4ATAC and RTTN Associated Syndromes