Figure 3.

Laminin-211 deficiency in diagnostic quadriceps muscle biopsies and chorionic villus biopsies. Complete laminin-211 deficiency in quadriceps muscle biopsy (A–D). Hematoxylin and eosin (H & E) stained section (A) shows marked dystrophic changes. Immunolabeling with the 300 kDa laminin-211 antibody (B) shows complete absence at the myofiber basal lamina (B, stars) and on an intramuscular motor nerve (B, arrow). There is widespread secondary upregulation of laminin alpha 5 (C), whereas labeling with the IIH6 antibody against the glycosylated alpha-dystroglycan epitope appears normal. Partial laminin-211 deficiency in quadriceps muscle biopsy (E–H). H&E stained section (E) shows moderate dystrophic changes. Immunolabeling with the 300 kDa laminin-211 antibody shows moderate, patchy reduction at the myofiber basal lamina (F) and complete absence on an intramuscular motor nerve (G, arrows). There is widespread secondary upregulation of laminin alpha 5 (H). Prenatal testing for laminin-211 deficiency in chorionic villus biopsies (I–M). Labeling of a positive control sample (fetus unaffected by LAMA2-RD) (I) with the 300 kDa laminin-211 antibody shows distinct membranous labeling at the trophoblastic basement membrane of chorionic villi. Example of a test case showing normal labeling (J,K) comparable to the positive control, and another case showing complete absence of laminin-211 at the trophoblastic basal lamina (L,M) of first-trimester chorionic villi. In this case, the complete absence of laminin-211 expression suggests that the fetus is affected by LAMA2-RD. Normal labeling for laminin-211 in chorionic villi does not exclude carrier status for LAMA2-RD.