Premium
Phosphoglycerate dehydrogenase (PHGDH) deficiency without epilepsy mimicking primary microcephaly
Author(s) -
Poli Antoine,
Vial Yoann,
Haye Damien,
Passemard Sandrine,
Schiff Manuel,
Nasser Hala,
Delanoe Catherine,
Cuadro Emma,
Kom Rémi,
Elanga Narcisse,
Favre Anne,
Drunat Séverine,
Verloes Alain
Publication year - 2017
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.38217
Subject(s) - microcephaly , compound heterozygosity , exome sequencing , epilepsy , spasticity , pediatrics , medicine , global developmental delay , genetics , biology , mutation , gene , psychiatry , physical therapy , phenotype
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.