Identification of a gene responsible for bilateral amastia with ectodermal dysplasia

Abstract

Although protein tyrosine phosphatase receptor type F (PTPRF) has been known to involve in human breast cancer and mouse mammary gland development, very little is known about its role in human mammary gland development. We identified a 18-year old Thai woman with bilateral absence of breasts and nipples, ectodermal dysplasia, and unilateral renal agenesis, who was found to have an inherited chromosomal balanced translocation, 46,XX,t(1;20)(p34.1;q13.13). High Density SNP-CGH Array analysis confirmed the normal DNA dosage. With fluorescent in situ hybridization analysis, the breakpoint on chromosome 1 was identified to interrupt the PTPRF gene. Although no apparent causative mutations or splicing defects were detected in the other allele of PTPRF, deficiency of its RNA and absence of its protein levels strongly suggest its involvement in the organs’ development. The proband’s unaffected mother and sisters, although harbored the same balanced translocated chromosome, did have a significant remaining level of PTPRF. Microsatellite analysis showed that the proband and her sisters inherited a different paternal chromosome. These findings suggest that the syndrome is inherited in an autosomal recessive manner. We, for the first time, present evidences that PTPRF plays an important role in human breast development. This finding could have implications on evolution of mammals, developmental biology of human mammary glands and malignancy of breast cancer.