Muscular dystrophy and myopathy_Paediatric
Gene: SOX8
Proband presented to genetics clinic at 27 years of age with BMI -3.4SD, height -2.7SD, head circumference -1.8SD. She had mild intellectual delay and clinical features of a congenital, nonprogressive myopathy with moderate proximal and distal weakness. X-rays showed skeletal dysplasia, including cervical thoracic scoliosis and lumbar scoliosis. She was reported as having had weakness at birth with poor suck, micrognathia, hypotonia, and talipes. She was documented to have significant motor delay as a child. MRI of the brain demonstrated large posterior fossa CSF spaces.
Muscle biopsy of the right medial gastrocnemius at age 1 demonstrated mild variation in fiber size with scattered, moderately small, rounded polyhedral fibers of both types. There were no significant dystrophic features.
Biallelic SOX8 variants biallelic (NM_014587.3:c.422+5G>C; c.583dup p.(His195ProfsTer11)) were identified by WGS. The +5 variant was shown to affect splicing, while the frameshift variant resulted in production of low-level truncated protein (not NMD predicted). Functional studies on patient fibroblasts showed misregulation of downstream SOX8 targets.
Sources: LiteratureCreated: 4 Jan 2024, 1:57 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Neurodevelopmental disorder (MONDO:0700092), SOX8-related
Publications
Variants in this GENE are reported as part of current diagnostic practice
Gene: sox8 has been classified as Red List (Low Evidence).
Gene: sox8 has been classified as Red List (Low Evidence).
gene: SOX8 was added gene: SOX8 was added to Muscular dystrophy and myopathy_Paediatric. Sources: Literature Mode of inheritance for gene: SOX8 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SOX8 were set to https://www.neurology.org/doi/full/10.1212/NXG.0000000000200088 Phenotypes for gene: SOX8 were set to Neurodevelopmental disorder (MONDO:0700092), SOX8-related Review for gene: SOX8 was set to RED gene: SOX8 was marked as current diagnostic