Refining the phenotype of SINO syndrome: A comprehensive cohort report of 14 novel cases.
Обработка статьи · этапы, ошибки и управление
Ошибки и ограничения
История · было → стало
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Alstrup Morten, Cesca Fabrizia, Krawczun-Rygmaczewska Alicja, López-Menéndez Celia, Pose-Utrilla Julia, Castberg Filip Christian, Bjerager Mia Ortved, Finnila Candice, Kruer Michael C, Bakhtiari Somayeh, Padilla-Lopez Sergio, Manwaring Linda, Keren Boris, Afenjar Alexandra, Galatolo Daniele, Scalise Roberta, Santorelli Fillippo M, Shillington Amelle, Vezain Myriam, Martinovic Jelena, Stevens Cathy, Gowda Vykuntaraju K, Srinivasan Varunvenkat M, Thiffault Isabelle, Pastinen Tomi, Baranano Kristin, Lee Angela, Granadillo Jorge, Glassford Megan R, Keegan Catherine E, Matthews Nicole, Saugier-Veber Pascale, Iglesias Teresa, Østergaard Elsebet
Аннотация
METHODS: In our international cohort, we have included 14 individuals, carrying 13 novel pathogenic KIDINS220 variants in heterozygous form. We assessed the clinical and molecular data of our cohort and previously reported individuals and, based on functional experiments, reached a better understanding of the pathogenesis behind the KIDINS220-related disease.
RESULTS: Using fetal tissue and in vitro assays, we demonstrate that the variants generate KIDINS220 truncated forms that mislocalize in punctate intracellular structures, with decreased levels of the full-length protein, suggesting a trans-dominant negative effect. A total of 92% had their diagnosis within 3 years, with symptoms of developmental delay, spasticity, hypotonia, lack of eye contact, and nystagmus. We identified a KIDINS220 variant associated with fetal hydrocephalus and show that 58% of examined individuals present brain ventricular dilatation. We extend the phenotypic spectrum of SINO syndrome to behavioral manifestations not previously highlighted.
CONCLUSION: Our study provides further insights into the clinical spectrum, etiology, and predicted functional impact of KIDINS220 variants.