The WNT10B gene encodes a member of the WNT family of secreted signaling proteins. The WNT10B protein mediates the canonical Wnt signaling pathway and thereby plays a role in several developmental processes. These include the regulation of adipocyte, chondrocyte and epithelial cell differentiation, hematopoietic stem cell proliferation, cell cycle arrest and cell fate commitment, apoptosis, skeletal muscle fiber development and bone trabecula formation. It is also involved in the cellular response to hydrostatic pressure, parathyroid hormone stimulus, retinoic acid and cAMP.
Mutations in this gene can thus have strong pathological consequences. WNT10B has been implicated in Split-Hand/Foot Malformation 6; (SHFM6), a rare limb disorder characterized by syndactyly and median clefts in the hands or feet. The gene has also been associated with Tooth Agenesis, Selective, 8 (STHAG8), a condition wherein affected individuals exhibit the congenital absence of several teeth in their permanent dentition.
The WNT10B gene is located on the long arm of chromosome 12. It spans a length of 6.5 kb of DNA and its coding sequence is spread across 6 exons. The gene encodes a 43 kDa protein product composed of 389 amino acids. An additional 20 kDa isoform of the WNT10B gene exists due to an alternatively spliced transcript variant. While the gene is widely expressed in the human body, overexpression is seen in heart, skeletal muscle and brain. Homozygous mutations in the gene have been associated with SHFM6 and heterozygous mutations have been linked to STHAG8.
Monies et al. (2017) characterized the genomic landscape of Saudi Arabia based on the findings of 1000 diagnostic panels and exomes. One patient, an 8-year-old female from a consanguineous family, presented with feet ectrodactyly, thumb polydactyly, left index camptodactyly and 2 missing digits in both feet. She also exhibited facial dysmorphic features such as hypertelorism and a broad nasal bridge. However, she had normal development. Using a multigene panel for dysmorphology/skeletal dysplasia, a homozygous mutation (c.338-1G>C) was identified in exon 4 of the patient’s WNT10B gene, associated with SHFM6. Given the atypical presentation of the patient, this case helped in the phenotypic expansion of the disorder.
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