Syndromic X-linked intellectual disability segregating with a missense variant in RLIM

European Journal of Human Genetics : EJHG
Elin TønneTorunn Fiskerstrand

Abstract

We describe a three-generation Norwegian family with a novel X-linked intellectual disability (XLID) syndrome characterized by subtle facial dysmorphism, autism and severe feeding problems. By exome sequencing we detected a rare missense variant (c.1067A>G, p.(Tyr356Cys)) in the RLIM gene, in two affected male second cousins. Sanger sequencing confirmed the presence of the variant in the four affected males (none of whom were siblings) and in three mothers available for testing. The variant was not present in 100 normal Norwegian controls, has not been reported in variant databases and is deleterious according to in silico prediction tools. The clinical phenotype and the variant co-segregate, yielding a LOD score of 3.0 for linkage to the shared region (36.09 Mb), which contains 242 genes. No other shared rare variants on the X chromosome were detected in the two affected exome-sequenced individuals, and all female carriers had an extremely skewed X-chromosome inactivation pattern. RLIM encodes RING zinc finger protein 12 (RNF12), an ubiquitin ligase that is essential for X inactivation in mice and that acts as a co-regulator of a range of transcription factors, particularly those containing a LIM homeodomain. Tyrosine in posit...Continue Reading

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Citations

Apr 5, 2017·Translational Psychiatry·M J MoenR A Poot
Apr 27, 2018·American Journal of Medical Genetics. Part a·Giovanni NeriRoger E Stevenson
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Nov 19, 2019·Frontiers in Cell and Developmental Biology·Feng Wang, Ingolf Bach
Nov 17, 2020·Frontiers in Physiology·Léa Lescouzères, Pascale Bomont

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