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Figure 1 | Orphanet Journal of Rare Diseases

Figure 1

From: Genetic basis of hyperlysinemia

Figure 1

Molecular and biochemical studies in hyperlysinemia patients. (A) Schematic representation of the lysine degradation pathway. Lysine can be degraded via two pathways. The pathway with L-pipecolic acid as an intermediate operates in brain and starts with oxidative deamination. The main pathway in other organs, however, proceeds via deamination with saccharopine as an intermediate. All genes known to operate in this pathway are indicated. ALDH7A1 is deficient in children with pyridoxine-dependent seizures [3]. GCDH is deficient in glutaric aciduria type 1 [4]. The intermediate 2-oxoadipate is metabolized by 2-oxoadipate dehydrogenase, resembling the TCA cycle enzyme complex 2-oxoglutarate dehydrogenase. The E1 subunit of this complex is encoded by DHTKD1 and is deficient in 2-aminoadipic and 2-oxoadipic aciduria [5]. (B) Immunoblot analysis of fibroblast homogenates of hyperlysinemia cases. Cell lysates of 2 control subjects and hyperlysinemia cases were resolved by SDS-PAGE (30 μg of protein) blotted onto nitrocellulose and analyzed with a polyclonal antibody against AASS. (C) Relative expression levels of AASS in fibroblasts determined using qPCR with a primer sets specific for the 5 (R) and 3 (S) part of the cDNA. Average and SD are provided for 3 control fibroblasts. ND denotes not detectable. Expression was normalized to the level of cyclophilin B (PPIB). (D) Electropherogram showing that the heterozygous c.460G>A mutation in patient 5 appears homozygous at the cDNA level, indicating nonsense mediated decay of the other allele (c.2076dup).

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