LAS1L encodes a protein with a critical role in ribosomal biogenesis. Loss of LAS1L in S cerevisiae disrupts the processing of the 47S pre-rRNA at the second intervening sequence (ITS2), which separates the 5.8S and 28S rRNA sequences and affects the biogenesis of the large 60S ribosomal subunit. This curation is focused on evidence for LAS1L in causing X linked syndromic intellectual disability (MONDO: 0020119), but this has also been referred to in the literature as Wilson-Turner syndrome (MONDO:0010665; MIM:309585). LAS1L is localized to chromosome Xq12. Currently, there are only 7 LAS1L variants reported in the literature, 2 of which were seen in affected males of two large families and the rest were seen in singleton cases (PMIDs: 1746601, 25644381, 27479843, 28135719, 24647030, 32193494). Notably, all of the reported LAS1L variants are missense changes thus far. As for genetic evidence, the case level and segregation data add up to a score of 1.7 total points. The available experimental evidence for LAS1L mainly focuses on this gene’s cellular function in ribosome biogenesis and cell cycle (PMIDs: 20647540, 22190735, 22083961). Hence, none of the experimental evidence was scored. Overall, currently there is limited evidence available for LAS1L and X-linked syndromic intellectual disability. This classification was approved by the ClinGen Intellectual Disability and Autism Gene Curation Expert Panel on 09/21/2021 (SOP Version 8).
The GenCC data are available free of restriction under a CC0 1.0 Universal (CC0 1.0) Public Domain Dedication. The GenCC requests that you give attribution to GenCC and the contributing sources whenever possible and appropriate. The accepted Flagship manuscript is now available from Genetics in Medicine (https://www.gimjournal.org/article/S1098-3600(22)00746-8/fulltext).
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