Athelia is a very rare entity that is defined by the absence of the 
nipple-areola complex. It can affect either sex and is mostly part of syndromes 
including other congenital or ectodermal anomalies, such as limb-mammary 
syndrome, scalp-ear-nipple syndrome, or ectodermal dysplasias. Here, we report 
on three children from two branches of an extended consanguineous Israeli Arab 
family, a girl and two boys, who presented with a spectrum of nipple anomalies 
ranging from unilateral hypothelia to bilateral athelia but no other 
consistently associated anomalies except a characteristic eyebrow shape. Using 
homozygosity mapping after single nucleotide polymorphism (SNP) array genotyping 
and candidate gene sequencing we identified a homozygous frameshift mutation in 
PTPRF as the likely cause of nipple anomalies in this family. PTPRF encodes a 
receptor-type protein phosphatase that localizes to adherens junctions and may 
be involved in the regulation of epithelial cell-cell contacts, peptide growth 
factor signaling, and the canonical Wnt pathway. Together with previous reports 
on female mutant Ptprf mice, which have a lactation defect, and disruption of 
one allele of PTPRF by a balanced translocation in a woman with amastia, our 
results indicate a key role for PTPRF in the development of the nipple-areola 
region.