A novel microdeletion in 1(p34.2p34.3), involving the SLC2A1 (GLUT1) gene, and severe delayed development

Abstract

A de novo 4.1‐megabase microdeletion of chromosome 1p34.2p34.3 has been identified by array‐based comparative genomic hybridization in a young male with severely delayed development, microcephaly, pronounced hypotonia, and facial dysmorphism. The deleted region encompasses 48 genes, among them the glucose transporter 1 (SLC2A1 or GLUT1) gene. The deletion of the GLUT1 gene was in line with the abnormal ratio of cerebrospinal fluid (CSF) glucose to blood glucose, indicative of GLUT1 deficiency syndrome (MIM #606777). GLUT1 deficiency syndrome is characterized by therapy‐resistant infantile seizures, developmental delay, acquired microcephaly, spasticity, ataxia, and a low concentration of glucose in the CSF. It is known that a ketogenic diet can lead to better control of seizures. This case study shows that identifying a microdeletion as the cause of learning disability is not only important for genetic counselling but might also lead to therapeutic intervention.

A de novo 1p34.2 microdeletion identifies the synaptic vesicle gene RIMS3 as a novel candidate for autism

“…The closest match is the recent report of a Dutch boy with a 4.1 Mb deletion that completely overlaps the deletion we report, with loss of an additional 14 genes including the glucose transporter gene SLC2A1 35. Overall, he has a more severe phenotype than our patient with severe mental retardation and hypotonia, ‘profound’ microcephaly and epilepsy, as well as heterotopia and ponto-cerebellar atrophy on brain imaging.…”

Yield of additional metabolic studies in neurodevelopmental disorders

“…In the patient with a glucose 1 transporter (GLUT1) defect, low CSF glucose levels with an abnormal blood/glucose CSF ratio was found. The clinical presentation with psychomotor retardation, severe hypotonia with stereotypic movements, and dysmorphic features including microcephaly 20 was, however, not consistent with classic GLUT1. Targeted Comparative Genomic Hybridization array analysis demonstrated a microdeletion of chromosome 1p34.2p34.3 including the GLUT1 gene.…”

Overlap of autism spectrum disorder and glucose transporter 1 deficiency syndrome associated with a heterozygous deletion at the 1p34.2 region

“…ASD phenotype has not been reported in patients with SLC2A1 mutation. To date, rare patients have been reported with a deletion including SLC2A1 [7,8]. Patients with a deletion had normal pre-and perinatal histories, but they had more severe clinical deficits, including early onset generalized seizures, prominent facial dysmorphism with acquired microcephaly, and delayed motor and language milestones.…”