Further delineation of the phenotype caused by biallelic variants in the WDR4 gene
Clin Genet. 2017-09-29; 93(2): 374-377
DOI: 10.1111/cge.13074
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1. Clin Genet. 2018 Feb;93(2):374-377. doi: 10.1111/cge.13074. Epub 2017 Sep 29.
Further delineation of the phenotype caused by biallelic variants in the WDR4
gene.
Trimouille A(1), Lasseaux E(1), Barat P(2), Deiller C(1), Drunat S(3)(4), Rooryck
C(1)(5), Arveiler B(1)(5), Lacombe D(1)(5).
Author information:
(1)Service de Génétique Médicale, CHU Bordeaux, Bordeaux, France.
(2)Service d’Endocrinologie Pédiatrique, CHU Bordeaux, Bordeaux, France.
(3)Département de Génétique, Hôpital Robert Debré, PROTECT, Paris, France.
(4)Hôpital Robert Debré, INSERM U1141, Paris, France.
(5)INSERM U1211 – Maladies Rares, Génétique et Métabolisme (MRGM), Université de
Bordeaux, Bordeaux, France.
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 m7 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.
© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
DOI: 10.1111/cge.13074
PMID: 28617965 [Indexed for MEDLINE]