Further delineation of the phenotype caused by biallelic variants in the WDR4 gene. Issue 2 (29th September 2017)

• Record Type: Journal Article
• Authors: Trimouille, A.; Lasseaux, E.; Barat, P.; Deiller, C.; Drunat, S.; Rooryck, C.; Arveiler, B.; Lacombe, D.
• Is Part Of: Clinical genetics. Volume 93:Issue 2(2018)
• Page Start: 374
• Page End: 377
• Publication Date: 2017-09-29
• Subjects: exome sequencing -- growth retardation -- microcephaly -- WDR4; Medical genetics -- Periodicals; 616.0420
• DOI: 10.1111/cge.13074
• Languages: English
• ISSNs: 0009-9163

Abstract

Abstract : Microcephalic primordial dwarfisms are a group of rare Mendelian disorders characterized by severe growth retardation and microcephaly. The molecular basis is heterogeneous, with disease‐causing genes implicated in different cellular functions. Recently, 2 patients were reported with the same homozygous variant in the WDR4 gene, coding for an enzyme responsible for the m 7 G46 post transcriptional modification of tRNA. We report here 2 sisters harboring compound heterozygous variants of WDR4 . Their phenotype differs from that of the first 2 described patients: they both have a severe microcephaly but only one of the 2 sisters had a head circumference at birth below −2 SD, their intellectual deficiency is less severe, and they have a growth hormone deficiency and a partial hypogonadotropic hypogonadotropism. One of the 2 variants is a frameshift mutation, and the other one is a missense occurring in the same nucleotide affected by the first reported pathogenic variant, which could therefore be a mutational hot spot. The description of these 2 sisters allow us to confirm that biallelic variants in the WDR4 gene can lead to a specific phenotype, characterized by severe growth retardation and microcephaly. Abstract : Further delineation of the WDR4 associated phenotype.