Mosaicism in Hartsfield syndrome

Area of Science:

• Genetics
• Developmental Biology
• Medical Research

Background:

• Hartsfield syndrome is a rare genetic disorder characterized by ectrodactyly and holoprosencephaly spectrum disorders, often with cleft lip and palate.
• The condition is typically caused by variants in the FGFR1 gene, leading to loss of function or dominant negative effects.

Purpose of the Study:

• To report a novel FGFR1 variant associated with Hartsfield syndrome in a family with two affected fetuses.
• To investigate the potential role of mosaicism in Hartsfield syndrome, including germline and somatic mosaicism.

Main Methods:

• Sanger sequencing was used to detect variants in the FGFR1 gene.
• Analysis included affected fetuses and parental DNA to identify mosaicism.

Main Results:

• A novel FGFR1 variant was identified in a family with Hartsfield syndrome.
• Somatic and germline mosaicism was detected in the father of the affected fetuses.
• Mosaicism was found in 3 of 35 (9%) reported families, suggesting it may be a relatively frequent occurrence.

Conclusions:

• Mosaicism, including germline and/or somatic mosaicism, may be a significant factor in Hartsfield syndrome.
• The findings have important implications for genetic counseling and risk assessment in families with Hartsfield syndrome.