Expansion of the phenotypic spectrum and description of molecular findings in a cohort of patients with oculocutaneous mosaic RASopathies

Autor: Daniel López-Moreno, Enriqueta Hofmann, Juan Carlos Zenteno, Oscar F. Chacon-Camacho, Vianney Cortés-González, Cristina Villanueva-Mendoza, Ilse Wieland, Michelle Pacheco‐Quito, Martha Alejandra Morales-Sánchez, Martin Zenker
Rok vydání: 2019
Předmět:
0301 basic medicine
Neuroblastoma RAS viral oncogene homolog
mucocutaneous hyperpigmentation
Pathology
medicine.medical_specialty
Eye Diseases
Lipomatosis
encephalo‐cranio‐cutaneous lipomatosis
Schimmelpenning‐Fuerstein‐Mims syndrome
Nevus
Sebaceous of Jadassohn
030105 genetics & heredity
medicine.disease_cause
GTP Phosphohydrolases
law.invention
Proto-Oncogene Proteins p21(ras)
03 medical and health sciences
symbols.namesake
Ectodermal Dysplasia
law
KRAS
Genetics
medicine
Humans
Receptor
Fibroblast Growth Factor
Type 1
HRAS
RASopathies
Molecular Biology
Genetics (clinical)
Polymerase chain reaction
Dermoid Cyst
Sanger sequencing
oculoectodermal syndrome
Massive parallel sequencing
Mosaicism
business.industry
Neurocutaneous Syndromes
Membrane Proteins
Original Articles
medicine.disease
Phenotype
FGFR1
030104 developmental biology
symbols
Original Article
business
Zdroj: Molecular Genetics & Genomic Medicine
ISSN: 2324-9269
DOI: 10.1002/mgg3.625
Popis: Background Postzygotic KRAS, HRAS, NRAS, and FGFR1 mutations result in a group of mosaic RASopathies characterized by related developmental anomalies in eye, skin, heart, and brain. These oculocutaneous disorders include oculoectodermal syndrome (OES) encephalo‐cranio‐cutaneous lipomatosis (ECCL), and Schimmelpenning‐Feuerstein‐Mims syndrome (SFMS). Here, we report the results of the clinical and molecular characterization of a novel cohort of patients with oculocutaneous mosaic RASopathies. Methods Two OES, two ECCL, and two SFMS patients were ascertained in the study. In addition, two subjects with unilateral isolated epibulbar dermoids were also enrolled. Molecular analysis included PCR amplification and Sanger sequencing of KRAS, HRAS, NRAS, and FGFR1 genes in DNA obtained from biopsies (skin/epibulbar dermoids), buccal mucosa, and blood leukocytes. Massive parallel sequencing was employed in two cases with low‐level mosaicism. Results In DNA from biopsies, mosaicism for pathogenic variants, including KRAS p.Ala146Thr in two OES subjects, FGFR1 p.Asn546Lys and KRAS p.Ala146Val in ECCL patients, and KRAS p.Gly12Asp in both SFMS patients, was demonstrated. No mutations were shown in DNA from conjunctival lesions in two subjects with isolated epibubar dermoids. Conclusion Our study allowed the expansion of the clinical spectrum of mosaic RASopathies and supports that mosaicism for recurrent mutations in KRAS and FGFR1 is a commonly involved mechanism in these rare oculocutaneous anomalies.
Databáze: OpenAIRE
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