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Title: Focal Facial Dermal Dysplasia, Type IV, is caused by mutations in CYP26C1
Authors: Slavotinek, Anne M ×
Mehrotra, Pavni
Nazarenko, Irina
Tang, Paul Ling-Fung
Lao, Richard
Cameron, Don
Li, Ben
Chu, Catherine
Chou, Chris
Marqueling, Ann L
Yahyavi, Mani
Cordoro, Kelly
Frieden, Ilona
Glaser, Tom
Prescott, Trine
Morren, Marie-Anne
Devriendt, Koenraad
Kwok, Pui-Yan
Petkovich, Martin
Desnick, Robert J #
Issue Date: Feb-2013
Publisher: IRL Press
Series Title: Human molecular genetics vol:22 issue:4 pages:696-703
Abstract: Focal facial dermal dysplasia (FFDD) Type IV is a rare syndrome characterized by facial lesions resembling aplasia cutis in a preauricular distribution along the line of fusion of the maxillary and mandibular prominences. To identify the causative gene(s), exome sequencing was performed in a family with two affected sibs. Assuming autosomal recessive inheritance, two novel sequence variants were identified in both sibs in CYP26C1 - a duplication of 7 basepairs that was maternally inherited, c.844_851dupCCATGCA, predicting p.Glu284fsX128, and a missense mutation, c.1433G>A, predicting p.Arg478His, that was paternally inherited. The duplication predicted a frameshift mutation that lead to a premature stop codon and premature chain termination, while the missense mutation was not functional based on its in-vitro expression in mammalian cells. The FFDD skin lesions arise along the sites of fusion of the maxillary and mandibular prominences early in facial development and Cyp26c1 was expressed exactly along the fusion line for these facial prominences in the first branchial arch in mice. Sequencing of four additional, unrelated Type IV FFDD patients and eight Type II or III TWIST2-negative FFDD patients revealed that three of the Type IV patients were homozygous for the duplication, whereas none of the Type II or III patients had CYP26C1 mutations. The 7 basepair duplication was present in 0.3% of healthy controls and 0.3% of patients with other birth defects. These findings suggest that the phenotypic manifestations of FFDD Type IV can be non-penetrant or under-ascertained. Thus, FFDD Type IV results from loss of function mutations in CYP26C1.
URI: 
ISSN: 0964-6906
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Department of Human Genetics - miscellaneous
× corresponding author
# (joint) last author

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