Homozygous truncating PTPRF mutation causes athelia.
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.
Institute of Human Genetics, University of Ulm, Ulm, Germany, guntram.borck@uni-ulm.de.
Guntram
G
Borck
Liat
L
de Vries
Hsin-Jung
HJ
Wu
Pola
P
Smirin-Yosef
Gudrun
G
Nürnberg
Irina
I
Lagovsky
Luis Henrique
LH
Ishida
Patrick
P
Thierry
Dagmar
D
Wieczorek
Peter
P
Nürnberg
John
J
Foley
Christian
C
Kubisch
Lina
L
Basel-Vanagaite
D000293:Adolescent; D000328:Adult; D000818:Animals; D001940:Breast / Q000002:abnormalities* / Q000473:pathology; D001941:Breast Diseases; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D000013:Congenital Abnormalities / Q000209:etiology* / Q000473:pathology; D005260:Female; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D016368:Frameshift Mutation / Q000235:genetics*; D020869:Gene Expression Profiling; D055106:Genome-Wide Association Study; D006720:Homozygote; D006801:Humans; D007223:Infant; D008297:Male; D051379:Mice; D009558:Nipples / Q000378:metabolism / Q000473:pathology; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2 / Q000235:genetics*
C516772:PTPRF protein, human; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2