مورد إلكتروني
Focal facial dermal dysplasia, type IV, is caused by mutations in CYP26C1.
| العنوان: | Focal facial dermal dysplasia, type IV, is caused by mutations in CYP26C1. |
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| المؤلفون: | Slavotinek, Anne M |
| المصدر: | Human molecular genetics; vol 22, iss 4, 696-703; 0964-6906 |
| بيانات النشر: | eScholarship, University of California 2013-02-01 |
| تفاصيل مُضافة: | 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, Koen Kwok, Pui-yan Petkovich, Martin Desnick, Robert J |
| نوع الوثيقة: | Electronic Resource |
| مستخلص: | 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 siblings. Assuming autosomal recessive inheritance, two novel sequence variants were identified in both siblings in CYP26C1-a duplication of seven base pairs, which 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 led to a premature stop codon and premature chain termination, whereas 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 seven base pairs 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 underascertained. Thus, FFDD Type IV results from the loss of function mutations in CYP26C1. |
| مصطلحات الفهرس: | COS Cells, Animals, Humans, Mice, Ectodermal Dysplasia, Cytochrome P-450 Enzyme System, DNA Mutational Analysis, Microsatellite Repeats, Frameshift Mutation, Mutation, Missense, Genetic Association Studies, Cytochrome P450 Family 26, Chlorocebus aethiops, Focal Facial Dermal Dysplasias, Congenital Structural Anomalies, Genetics, Biotechnology, Clinical Research, Pediatric, 2.1 Biological and endogenous factors, Aetiology, Congenital, Biological Sciences, Medical and Health Sciences, Genetics & Heredity, article |
| URL: | |
| الإتاحة: | Open access content. Open access content public |
| ملاحظة: | application/pdf Human molecular genetics vol 22, iss 4, 696-703 0964-6906 |
| أرقام أخرى: | CDLER oai:escholarship.org:ark:/13030/qt0bq0m7jv qt0bq0m7jv https://escholarship.org/uc/item/0bq0m7jvTest https://escholarship.orgTest/ 1377978708 |
| المصدر المساهم: | UC MASS DIGITIZATION From OAIster®, provided by the OCLC Cooperative. |
| رقم الانضمام: | edsoai.on1377978708 |
| قاعدة البيانات: | OAIster |
| الوصف غير متاح. |