HNRNPA1 de novo Variant Associated with Early Childhood Onset, Rapidly Progressive Generalized Myopathy.

HNRNPA1 variants are known to cause degenerative motoneuron and muscle diseases which manifests in middle age or later. We report on a girl with early childhood onset, rapidly progressive generalized myopathy including ultrastructural findings in line with a proteinopathy. Proteomics of patient-derived muscle and combined screening of genomic data for copy number variations identified a HNRNPA1 de novo intragenic deletion as causative for the phenotype.

Variant of the catalytic cysteine of UFSP2 leads to spondyloepimetaphyseal dysplasia type Di Rocco.

Spondyloepimetaphyseal dysplasia (SEMD) is characterized by vertebral, epiphyseal, and metaphyseal alterations. Patients become predominantly apparent with disproportionate short stature. The genetic background of SEMD is heterogeneous, with different modes of inheritance (autosomal dominant, autosomal recessive, and X-linked disorders).