Results: 3

1.
Figure 1

Figure 1. Pedigree and Distribution of GNPTAB Glu1200Lys Mutation in Family PKST72. From: Mutations in the Lysosomal Enzyme–Targeting Pathway and Persistent Stuttering.

Subjects 77 and 89 (green ovals) were homozygous for the mutation but were unaffected, suggesting nonpenetrance. Subjects 65, 69, and 83 (pink ovals) were affected but differed from the other affected subjects with respect to the haplotype surrounding the gene for the alpha and beta subunits of N-acetylglucosamine-1-phosphate transferase (GNPTAB). Double lines indicate consanguineous unions. Squares denote male family members, circles female members, solid symbols affected members, and slashes deceased members.

Changsoo Kang, et al. N Engl J Med. ;362(8):677-685.
2.
Figure 3

Figure 3. Tagging for Transport of Lysosomal Enzyme. From: Mutations in the Lysosomal Enzyme–Targeting Pathway and Persistent Stuttering.

In the first step, GlcNAc-phosphotransferase (the alpha, beta, and gamma subunits of which are encoded by the GNPTAB and GNPTG genes) catalyzes the covalent linkage of GlcNAc-1-phosphate from uridine diphosphate (UDP) to the terminal mannose residues of the N-linked oligosaccharides on enzymes destined for the lysosome. In the second step, NAGPA (N-acetylglucosamine-1-phosphodiester alpha-N-acetylglucosaminidase), also known as uncovering enzyme, removes one GlcNAc group, thereby exposing mannose-6-phosphate (M6P), which acts as the targeting signal. Enzymes with this targeting signal are then routed through the Golgi apparatus to the lysosome.

Changsoo Kang, et al. N Engl J Med. ;362(8):677-685.
3.
Figure 2

Figure 2. Mutations Found in GNPTAB, GNPTG, and NAGPA and Alignment of Their Amino Acid Sequences in Different Species. From: Mutations in the Lysosomal Enzyme–Targeting Pathway and Persistent Stuttering.

Shaded areas indicate amino acid changes resulting from mutations in various species. In NAGPA, p.Phe513SerfsX113 denotes a frame-shift mutation that changes phenylalanine 513 to serine and creates a new reading frame that ends in a stop 113 amino acids downstream (see , available with the full text of this article at NEJM.org). GNPTAB denotes the N-acetylglucosamine-1-phosphate transferase gene encoding the subunits alpha and beta, GNPTG the N-acetylglucosamine-1-phosphate transferase gene encoding the subunit gamma, and NAGPA the N-acetylglucosamine-1-phosphodiester alpha-N-acetylglucosaminidase gene.

Changsoo Kang, et al. N Engl J Med. ;362(8):677-685.

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