A novel EXT2 mutation in a consanguineous family with severe developmental delay, microcephaly, seizures, feeding difficulties, and osteopenia extends the phenotypic spectrum of autosomal recessive EXT2-related syndrome (AREXT2)

Lara El-Bazzal (1) , Alexandre Atkinson (1) , Anne-Celine Gillart (2) , Marc Obeid (3) , Valérie Delague (1) , André Mégarbané (2)

1 MMG - Marseille medical genetics - Centre de génétique médicale de Marseille
2 Institut Jérôme Lejeune
3 AUST - American University of Science and Technology

We report a consanguineous family where 2 boys presented with developmental delay, hypotonia, microcephaly, seizures, gastro-intestinal abnormalities, osteopenia, and neurological regression. Whole exome sequencing performed in one of the boys revealed the presence of a novel homozygous missense variant in the EXT2 gene: c.11C > T (p.Ser4Leu). Segregation analysis by Sanger sequencing confirmed homozygous by descent autosomal recessive transmission of this mutation. Another family was previously reported with homozygous mutations in this gene in four siblings affected with a nearly similar clinical condition (Farhan et al., 2015). We discuss the similarities and differences between the two syndromes and propose AREXT2 as a new acronym for EXT2-related diseases.

Mots clés: Intellectual deficiency; Seizures; Recessive; EXT2; Mutation; AREXT2; Homozygous

Domaines: Génétique

Lara El-Bazzal, Alexandre Atkinson, Anne-Celine Gillart, Marc Obeid, Valérie Delague, et al.. A novel EXT2 mutation in a consanguineous family with severe developmental delay, microcephaly, seizures, feeding difficulties, and osteopenia extends the phenotypic spectrum of autosomal recessive EXT2-related syndrome (AREXT2). European Journal of Medical Genetics, 2018, 62 (4), pp.259-264. ⟨10.1016/j.ejmg.2018.07.025⟩. ⟨hal-01984013⟩