Phenotypic and mutational spectrum of ROR2-related Robinow syndrome.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Lima Ariadne R, Ferreira Barbara M, Zhang Chaofan, Jolly Angad, Du Haowei, White Janson J, Dawood Moez, Lins Tulio C, Chiabai Marcela A, van Beusekom Ellen, Cordoba Mara S, Caldas Rosa Erica C C, Kayserili Hulya, Kimonis Virginia, Wu Erica, Mellado Cecilia, Aggarwal Vineet, Richieri-Costa Antonio, Brunoni Décio, Canó Talyta M, Jorge Alexander A L, Kim Chong A, Honjo Rachel, Bertola Débora R, Dandalo-Girardi Raissa M, Bayram Yavuz, Gezdirici Alper, Yilmaz-Gulec Elif, Gumus Evren, Yilmaz Gülay C, Okamoto Nobuhiko, Ohashi Hirofumi, Coban-Akdemir Zeynep, Mitani Tadahiro, Jhangiani Shalini N, Muzny Donna M, Regattieri Neysa A P, Pogue Robert, Pereira Rinaldo W, Otto Paulo A, Gibbs Richard A, Ali Bassam R, van Bokhoven Hans, Brunner Han G, Sutton V Reid, Lupski James R, Vianna-Morgante Angela M, Carvalho Claudia M B, Mazzeu Juliana F
Аннотация
Robinow syndrome is characterized by a triad of craniofacial dysmorphisms, disproportionate-limb short stature, and genital hypoplasia. A significant degree of phenotypic variability seems to correlate with different genes/loci. Disturbances of the noncanonical WNT-pathway have been identified as the main cause of the syndrome. Biallelic variants in ROR2 cause an autosomal recessive form of the syndrome with distinctive skeletal findings. Twenty-two patients with a clinical diagnosis of autosomal recessive Robinow syndrome were screened for variants in ROR2 using multiple molecular approaches. We identified 25 putatively pathogenic ROR2 variants, 16 novel, including single nucleotide variants and exonic deletions. Detailed phenotypic analyses revealed that all subjects presented with a prominent forehead, hypertelorism, short nose, abnormality of the nasal tip, brachydactyly, mesomelic limb shortening, short stature, and genital hypoplasia in male patients. A total of 19 clinical features were present in more than 75% of the subjects, thus pointing to an overall uniformity of the phenotype. Disease-causing variants in ROR2, contribute to a clinically recognizable autosomal recessive trait phenotype with multiple skeletal defects. A comprehensive quantitative clinical evaluation of this cohort delineated the phenotypic spectrum of ROR2-related Robinow syndrome. The identification of exonic deletion variant alleles further supports the contention of a loss-of-function mechanism in the etiology of the syndrome.