Molecular pathology of the fibroblast growth factor family

Area of Science:

• Molecular Biology
• Genetics
• Developmental Biology

Background:

• The human fibroblast growth factor (FGF) family comprises 22 proteins crucial for physiological processes in development and adulthood.
• FGF gene mutations were not initially linked to human diseases until FGF23 mutations caused hypophosphatemic rickets in 2000.
• Since 2000, mutations in seven FGF genes have been associated with distinct human disorders.

Purpose of the Study:

• To review the current understanding of the molecular pathology of the FGF family in human diseases.
• To highlight the diverse range of disorders linked to specific FGF gene mutations.
• To explore the functional consequences, inheritance patterns, and developmental effects of FGF mutations.

Main Methods:

• Literature review of studies on FGF gene mutations and associated human diseases.
• Compilation of known FGF gene mutations and their corresponding clinical manifestations.
• Analysis of the heterogeneity in disease presentation and inheritance patterns.

Main Results:

• Mutations in FGF3 are linked to Michel aplasia.
• FGF8 mutations are associated with cleft lip/palate and hypogonadotropic hypogonadism.
• FGF9 mutations are implicated in carcinoma.
• FGF10 mutations are linked to lacrimal/salivary glands aplasia and lacrimo-auriculo-dento-digital syndrome.
• FGF14 mutations are associated with spinocerebellar ataxia.
• FGF20 mutations are linked to Parkinson disease.
• FGF23 mutations are associated with tumoral calcinosis and hypophosphatemic rickets.

Conclusions:

• FGF gene mutations represent a significant cause of diverse human genetic disorders.
• The varied functional impacts, inheritance modes, and tissue specificities of FGF mutations offer insights into FGF signaling.
• Further research into FGF molecular pathology is essential for understanding and potentially treating these conditions.