A Novel Homozygous T-Cell Immune Regulator 1 (TCIRG1) Stop-Gain Variant Causing Malignant Infantile Osteopetrosis.

Malignant infantile osteopetrosis (MIOP) is a rare life-threatening autosomal recessive disorder characterized by defective osteoclast-mediated bone resorption, most commonly caused by pathogenic variants in the TCIRG1 gene. Without hematopoietic stem cell transplantation (HSCT), the disease is associated with severe morbidity and early mortality. We report a 15-month-old Moroccan girl born to first-cousin consanguineous parents who initially presented during infancy with failure to thrive, persistent bicytopenia, developmental delay, axial hypotonia, divergent strabismus with nystagmus, and facial dysmorphism. Skeletal radiographs demonstrated diffuse osteosclerosis, obliteration of medullary cavities, and characteristic Erlenmeyer flask deformities, strongly suggestive of MIOP. Whole-exome sequencing identified a novel homozygous pathogenic variant in T-cell immune regulator 1 (TCIRG1) (NM_006019.4:c.1897C>T; p.Gln633Ter). The variant is absent from the gnomAD database and was classified as pathogenic according to the American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) criteria. To the best of our knowledge, this variant has not previously been reported in affected individuals. The patient is currently undergoing evaluation for HSCT. This case expands the mutational spectrum of TCIRG1-associated MIOP and highlights the importance of early genomic testing in infants from consanguineous families presenting with unexplained cytopenias, growth failure, and characteristic skeletal abnormalities.