Phosphoglycerate dehydrogenase (PHGDH) deficiency without epilepsy mimicking primary microcephaly.

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.

Genetic modulators of sickle cell disease in French Guiana: Markers of the slave trade.

OBJECTIVES: Sickle cell disease (SCD) is the leading genetic disease in French Guiana, reflecting the predominantly African ancestry of the Guianese population. Our purpose was to characterize the genetic modulators of SCD in order to retrace the origin of the population in light of the slave trade. METHODS: We have studied the sickle cell genotype, the ßS haplotypes, the alpha and beta thalassemia and the UGT1A1 promoter polymorphisms in 224 Guianese patients with SCD. RESULTS: The genotypes of SCD were HbSS 65.6%, HbSC 24.5%, and HbS-beta thalassemia 9.4%. The most frequent ßS haplotypes were the Benin haplotype (65.9% of the chromosomes) and the Bantu (20.5%). Alpha thalassemic deletions were present in 37% of the patients and homozygosity for the (TA)7 allele of the UGT1A1 promoter in 21.4%. When the patients' origins were considered, 3 groups, Noir Marron, Haitians and Creoles, displayed distinctive characteristics. The HbSC genotype, the Benin haplotype, and the homozygous UGT1A1 genotype TA7/TA7 were significantly more frequent in Noir Marron. The Haitian patients were characterized by the occurrence of alpha-thalassemia and beta-thalassemia and by a higher prevalence of the Bantu haplotype. In the group of Creole patients, the genotype HbSS was predominant but the other modulators of SCD were associated with intermediate risk. CONCLUSIONS: The results highlight the genetic diversity of the Guianese population and are concordant with historical data on the slave trade showing a West African origin for Noir Marron and a Central African origin for Haitians, while Guianese Creoles are highly admixed. Am. J. Hum. Biol. 28:811-816, 2016. © 2016Wiley Periodicals, Inc.