Osteopathia Striata with Cranial Sclerosis: A Face-to-Radiograph-to-Gene Diagnosis

Arora, Veronica; Saxena, K. K.; Suman, Praveen; Kukreja, Shyam

doi:10.1055/s-0040-1715120

Cited by 2 publications

(1 citation statement)

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“…Five genes with recurrent mutations were identified, with a missense mutation (c.61C>T: p.R21C) in AMER1, the gene encoding APC membrane recruitment protein 1, detected in two families and predicted to be "Damaging" by both SIFT and Polyphen-2. AMER1, which is located on the X chromosome in humans, specifically at Xq11, has been shown to be the pathological gene responsible for osteopathia striata with cranial sclerosis (OSCS, MIM: 300373) [5], an X-linked dominant developmental disease manifesting mainly in females as macrocephaly, cleft palate, mild learning disabilities, sclerosis of the long bones and skull, and longitudinal striations visible on radiographs of the bones [6]. The disorder is usually considered lethal in males.…”

Section: Introductionmentioning

confidence: 99%

amer1 Regulates Zebrafish Craniofacial Development by Interacting with the Wnt/β-Catenin Pathway

Sun,

Ping,

Fan

et al. 2024

IJMS

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Microtia-atresia is a rare type of congenital craniofacial malformation causing severe damage to the appearance and hearing ability of affected individuals. The genetic factors associated with microtia-atresia have not yet been determined. The AMER1 gene has been identified as potentially pathogenic for microtia-atresia in two twin families. An amer1 mosaic knockdown zebrafish model was constructed using CRISPR/Cas9. The phenotype and the development process of cranial neural crest cells of the knockdown zebrafish were examined. Components of the Wnt/β-catenin pathway were examined by qPCR, Western blotting, and immunofluorescence assay. IWR-1-endo, a reversible inhibitor of the Wnt/β-catenin pathway, was applied to rescue the abnormal phenotype. The present study showed that the development of mandibular cartilage in zebrafish was severely compromised by amer1 knockdown using CRISPR/Cas9. Specifically, amer1 knockdown was found to affect the proliferation and apoptosis of cranial neural crest cells, as well as their differentiation to chondrocytes. Mechanistically, amer1 exerted an antagonistic effect on the Wnt/β-catenin pathway. The application of IWR-1-endo could partially rescue the abnormal phenotype. We demonstrated that amer1 was essential for the craniofacial development of zebrafish by interacting with the Wnt/β-catenin pathway. These findings provide important insight into the role of amer1 in zebrafish mandibular development and the pathology of microtia-atresia caused by AMER1 gene mutations in humans.

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Section: Introductionmentioning

confidence: 99%