Out-of-frame translation rescues a loss-of-function variant in a novel TBCE phenotype.

Context: Pathogenic variants in the TBCE gene, encoding tubulin-specific chaperone E crucial for tubulin folding, are linked to three severe neurodevelopmental disorders: Hypoparathyroidism-retardation-dysmorphism (HRD) syndrome, Kenny-Caffey syndrome type 1, and progressive encephalopathy with amyotrophy and optic atrophy.

Objective: We identified patients with a novel, milder TBCE-associated phenotype and aimed to characterize it at the clinical and molecular levels.

Materials And Methods: We conducted splicing analysis using deep NGS sequencing of RT-PCR products and detected TBCE through Western blotting.

Masks of Albinism: Clinical Spectrum of Hermansky-Pudlak Syndrome.

Hermansky-Pudlak syndrome (HPS) is a rare disease inherited in the autosomal recessive mode, including 11 clinical genetic subtypes. They are associated with impaired function of the BLOC protein complex (Biogenesis of Lysosome-related Organelles Complexes), and the subunits of the AP-3 complex (adaptor protein complex). Each has its own clinical features, but they are all characterized by albinism, bleeding disorder, and visual abnormalities.

Cases report: Mosaic structural variants of the gene in previously genetically unconfirmed multiple osteochondromas.

Multiple osteochondromas (MO) is a rare autosomal dominant skeletal disorder characterized by the development of multiple benign tumors known as osteochondromas. The condition is predominantly caused by loss-of-function variants in the or genes, facilitating relatively precise clinical diagnosis through established diagnostic criteria. Despite this, a notable percentage of MO cases (10%-20%) remains unresolved after sequencing coding regions and copy number analysis of both genes.

[Developmental and epileptic encephalopathy produced by the ATP1A2 mutation].

A case of DEE98, a rare developmental and epileptic encephalopathy related to previously reported the missense mutation p.Arg908Gln in the gene, is described. A girl examined first time in 11 months had microcephaly, severe mental and motor delay, strabismus, spastic paraparesis and pachypolymicrogyria on brain MRI that is atypical for DEE98.