J Urban1, L Qi2, H Zhao3, I Rybak1, K A Rauen4, M Kiuru1,5. 1. Department of Dermatology, University of California, Davis, Sacramento, CA, USA. 2. Department of Public Health Sciences, University of California, Davis, Davis, CA, USA. 3. Department of Food Science, Zhejiang University, Hangzhou, China. 4. Department of Pediatrics, University of California, Davis, Sacramento, CA, USA. 5. Department of Pathology and Laboratory Medicine, University of California, Davis, Sacramento, CA, USA.
Abstract
BACKGROUND: Abnormal hair growth is a defining feature of RASopathies, syndromes caused by germline mutations in the RAS pathway. However, detailed hair manifestations and the mechanisms of altered hair growth in RASopathies are poorly delineated. OBJECTIVES: To identify distinguishing clinical features and investigate how the RAS pathway influences hair growth by performing a systematic and detailed side-by-side comparison of hair manifestations in cardio-facio-cutaneous syndrome (CFCS) and Costello syndrome (CS), two RASopathies caused by mutations in the downstream and upstream elements of the RAS pathway, respectively. METHODS: Sixteen individuals with CFCS and 23 individuals with CS were enrolled. Mutation data were recorded. Scalp hair, eyebrows and eyelashes of individuals with CFCS or CS were examined for texture, colour, density and morphology. Scalp hairs were examined by light microscopy. RESULTS: While both syndromes displayed abnormal hair, striking differences were observed, including darker and thicker scalp hair and sparse eyebrows and eyelashes in CFCS. By contrast, synophrys, trichomegaly and abnormalities of the scalp hair shafts were observed in CS. Possible correlation with straight hair and genotype was observed in CS. CONCLUSION: The results emphasize the role of the RAS pathway in hair growth, improve accuracy of clinical diagnosis of CFCS and CS and provide a foundation for identification of therapeutic targets.
BACKGROUND: Abnormal hair growth is a defining feature of RASopathies, syndromes caused by germline mutations in the RAS pathway. However, detailed hair manifestations and the mechanisms of altered hair growth in RASopathies are poorly delineated. OBJECTIVES: To identify distinguishing clinical features and investigate how the RAS pathway influences hair growth by performing a systematic and detailed side-by-side comparison of hair manifestations in cardio-facio-cutaneous syndrome (CFCS) and Costello syndrome (CS), two RASopathies caused by mutations in the downstream and upstream elements of the RAS pathway, respectively. METHODS: Sixteen individuals with CFCS and 23 individuals with CS were enrolled. Mutation data were recorded. Scalp hair, eyebrows and eyelashes of individuals with CFCS or CS were examined for texture, colour, density and morphology. Scalp hairs were examined by light microscopy. RESULTS: While both syndromes displayed abnormal hair, striking differences were observed, including darker and thicker scalp hair and sparse eyebrows and eyelashes in CFCS. By contrast, synophrys, trichomegaly and abnormalities of the scalp hair shafts were observed in CS. Possible correlation with straight hair and genotype was observed in CS. CONCLUSION: The results emphasize the role of the RAS pathway in hair growth, improve accuracy of clinical diagnosis of CFCS and CS and provide a foundation for identification of therapeutic targets.
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Authors: Elizabeth M McCormick; Elizabeth Hopkins; Laura Conway; Sarah Catalano; Jobayer Hossain; Katia Sol-Church; Deborah L Stabley; Karen W Gripp Journal: Genet Med Date: 2013-02-21 Impact factor: 8.822
Authors: Maija Kiuru; Jennifer Urban; Guannan Zhu; Iryna Rybak; Jessica R Terrell; Lihong Qi; John D McPherson; Ashfaq A Marghoob; Katherine A Rauen Journal: J Am Acad Dermatol Date: 2020-01-27 Impact factor: 11.527
Authors: Maria I Kontaridis; Amy E Roberts; Lisa Schill; Lisa Schoyer; Beth Stronach; Gregor Andelfinger; Yoko Aoki; Marni E Axelrad; Annette Bakker; Anton M Bennett; Alberto Broniscer; Pau Castel; Caitlin A Chang; Lukas Cyganek; Tirtha K Das; Jeroen den Hertog; Emilia Galperin; Shruti Garg; Bruce D Gelb; Kristiana Gordon; Tamar Green; Karen W Gripp; Maxim Itkin; Maija Kiuru; Bruce R Korf; Jeff R Livingstone; Alejandro López-Juárez; Pilar L Magoulas; Sahar Mansour; Theresa Milner; Elisabeth Parker; Elizabeth I Pierpont; Kevin Plouffe; Katherine A Rauen; Suma P Shankar; Shane B Smith; David A Stevenson; Marco Tartaglia; Richard Van; Morgan E Wagner; Stephanie M Ware; Martin Zenker Journal: Am J Med Genet A Date: 2022-03-09 Impact factor: 2.578