Homozygous truncating PTPRF mutation causes athelia
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Homozygous truncating PTPRF mutation causes athelia. / Borck, Guntram; de Vries, Liat; Wu, Hsin-Jung; Smirin-Yosef, Pola; Nürnberg, Gudrun; Lagovsky, Irina; Ishida, Luis Henrique; Thierry, Patrick; Wieczorek, Dagmar; Nürnberg, Peter; Foley, John; Kubisch, Christian; Basel-Vanagaite, Lina.
In: HUM GENET, Vol. 133, No. 8, 01.08.2014, p. 1041-7.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Homozygous truncating PTPRF mutation causes athelia
AU - Borck, Guntram
AU - de Vries, Liat
AU - Wu, Hsin-Jung
AU - Smirin-Yosef, Pola
AU - Nürnberg, Gudrun
AU - Lagovsky, Irina
AU - Ishida, Luis Henrique
AU - Thierry, Patrick
AU - Wieczorek, Dagmar
AU - Nürnberg, Peter
AU - Foley, John
AU - Kubisch, Christian
AU - Basel-Vanagaite, Lina
PY - 2014/8/1
Y1 - 2014/8/1
N2 - 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.
AB - 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.
KW - Adolescent
KW - Adult
KW - Animals
KW - Breast
KW - Cells, Cultured
KW - Child
KW - Child, Preschool
KW - Congenital Abnormalities
KW - Female
KW - Fibroblasts
KW - Frameshift Mutation
KW - Gene Expression Profiling
KW - Genome-Wide Association Study
KW - Homozygote
KW - Humans
KW - Infant
KW - Male
KW - Mice
KW - Nipples
KW - Pedigree
KW - Polymorphism, Single Nucleotide
KW - Receptor-Like Protein Tyrosine Phosphatases, Class 2
U2 - 10.1007/s00439-014-1445-1
DO - 10.1007/s00439-014-1445-1
M3 - SCORING: Journal article
C2 - 24781087
VL - 133
SP - 1041
EP - 1047
JO - HUM GENET
JF - HUM GENET
SN - 0340-6717
IS - 8
ER -