Novel CYP4F22 mutations associated with autosomal recessive congenital ichthyosis (ARCI). Study of the CYP4F22 c.1303C>T founder mutation
Por:
Esperón-Moldes U, Ginarte-Val M, Rodríguez-Pazos L, Fachal L, Martín-Santiago A, Vicente-Villa MA, Jiménez-Gallo D, Guillén-Navarro E, Sampol LM, González-Enseñat MA and Vega A
Publicada:
18 feb 2020
Categoría:
Multidisciplinary
Resumen:
Mutations in CYP4F22 cause autosomal recessive congenital ichthyosis (ARCI). However, less than 10% of all ARCI patients carry a mutation in CYP4F22. In order to identify the molecular basis of ARCI among our patients (a cohort of ninety-two Spanish individuals) we performed a mutational analysis using direct Sanger sequencing in combination with a multi-gene targeted NGS panel. From these, eight ARCI families (three of them with Moroccan origin) were found to carry five different CYP4F22 mutations, of which two were novel. Computational analysis showed that the mutations found were present in highly conserved residues of the protein and may affect its structure and function. Seven of the eight families were carriers of a highly recurrent CYP4F22 variant, c.1303C>T; p.(His435Tyr). A 12Mb haplotype was reconstructed in all c.1303C>T carriers by genotyping ten microsatellite markers flanking the CYP4F22 gene. A prevalent 2.52Mb haplotype was observed among Spanish carrier patients suggesting a recent common ancestor. A smaller core haplotype of 1.2Mb was shared by Spanish and Moroccan families. Different approaches were applied to estimate the time to the most recent common ancestor (TMRCA) of carrier patients with Spanish origin. The age of the mutation was calculated by using DMLE and BDMC2. The algorithms estimated that the c.1303C>T variant arose approximately 2925 to 4925 years ago, while Spanish carrier families derived from a common ancestor who lived in the XIII century. The present study reports five CYP4F22 mutations, two of them novel, increasing the number of CYP4F22 mutations currently listed. Additionally, our results suggest that the recurrent c.1303C>T change has a founder effect in Spanish population and c.1303C>T carrier families originated from a single ancestor with probable African ancestry.
Filiaciones:
Esperón-Moldes U:
Fundación Pública Galega de Medicina Xenómica-SERGAS, Grupo de Medicina Xenómica-USC, CIBERER, IDIS, Santiago de Compostela, Spain
Departamento de Ciencias Forenses, Anatomía Patolóxica, Xinecoloxía, Obstetricia e Pediatría, Universidade de Santiago de Compostela, Santiago de Compostela, Spain
Ginarte-Val M:
Dermatology Service of Complexo Hospitalario Universitario de Santiago, Santiago de Compostela, Spain
Rodríguez-Pazos L:
Dermatology Service of Complexo Hospitalario Universitario de Vigo, Vigo, Spain
Fachal L:
Fundación Pública Galega de Medicina Xenómica-SERGAS, Grupo de Medicina Xenómica-USC, CIBERER, IDIS, Santiago de Compostela, Spain
Martín-Santiago A:
Dermatology Service of Hospital Universitari Son Espases, Palma de Mallorca, Spain
Vicente-Villa MA:
Dermatology Service of Hospital Sant Joan de Déu, Barcelona, Spain
Jiménez-Gallo D:
Dermatology Service of Hospital Puerta del Mar, Cádiz, Spain
Guillén-Navarro E:
Dermatology Service of Hospital clínico universitario Virgen de la Arrixaca, Murcia, Spain
Sampol LM:
Genetic Service of Hospital Sant Joan de Déu, Barcelona, Spain
González-Enseñat MA:
Dermatology Service of Hospital Sant Joan de Déu, Barcelona, Spain
Vega A:
Fundación Pública Galega de Medicina Xenómica-SERGAS, Grupo de Medicina Xenómica-USC, CIBERER, IDIS, Santiago de Compostela, Spain
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