Phosphoglycerate dehydrogenase (PHGDH) deficiency without epilepsy mimicking primary microcephaly.
Antoine PoliYoann VialDamien HayeSandrine PassemardManuel SchiffHala NasserCatherine DelanoeEmma CuadroRémi KomNarcisse ElangaAnne FavreSéverine DrunatAlain VerloesPublished in: American journal of medical genetics. Part A (2017)
Phosphoglycerate dehydrogenase (PHGDH) deficiency (OMIM 256520) is a rare autosomal recessive disorder of serine synthesis, with mostly severe congenital microcephaly, caused by mutations in the PHGDH gene. Fourteen patients reported to date show severe, early onset, drug resistant epilepsy. In a cohort of patients referred for primary microcephaly, compound heterozygosity for two unreported variants in PHGDG was identified by exome sequencing in a pair of sibs who died aged 4.5 months and 4.5 years. They had severe neurological involvement with congenital microcephaly, disorganized EEG, and progressive spasticity, but never had seizures. Exome usage in clinical practice is likely to lead to an expansion of the clinical spectrum of known disorders.
Keyphrases
- early onset
- zika virus
- drug resistant
- intellectual disability
- end stage renal disease
- ejection fraction
- copy number
- newly diagnosed
- multidrug resistant
- prognostic factors
- peritoneal dialysis
- dna methylation
- gene expression
- patient reported outcomes
- blood brain barrier
- working memory
- protein kinase
- subarachnoid hemorrhage
- high density
- genome wide identification