First prenatal diagnosis of defects in the HsPDX1 gene encoding protein X,an additional lipoyl-containing subunit of the human pyruvate dehydrogenase complex

We have previously reported a genetic study of a neonatal lactic acidosis l inked to a pyruvate dehydrogenase complex deficiency due to the absence of the protein X subunit. This rare autosomal recessive disorder is associated with specific deletions in this polypeptide which is encoded by the HsPDX1 gene, located on chromosome 11p1.3. The pathology of the patient was consi dered to arise from a large homozygous deletion (78del85) found at the 5' e nd of the HsPDX1 coding sequence. Her heterozygous mother underwent prenata l diagnosis during a subsequent pregnancy. Chorionic villus samples were us ed for three independent studies: (1) normal levels of the protein X compon ent of the PDH complex were detected by immunoblotting; (2) RT-PCR analysis showed no deletion at the 5' end of the cDNA but the presence of a distinc t heterozygous deletion (965del59) at its 3' end inherited from the father; (3) haplotype analysis revealed the presence of the father's mutated allel e and the mother's normal allele. It was concluded that the fetus was heter ozygous for this separate 3' deletion, so, it was likely to be not affected . This study permitted us to characterize more precisely the genetic abnorm alities of the HsPDX1 cDNA occurring in each family's member. Copyright (C) 1999 John Wiley & Sons, Ltd.