Fig. 1

Clinical features and mutations. a Pedigree of Family 1 showing the proband (arrow), similarly affected older female sibling and affected fetus. DNA-sequencing chromatograms demonstrate a homozygous four nucleotide deletion at the 3′-end of FXR1 exon-15 in the proband, which is in the heterozygous state in his mother (carrier). Carrier chromatogram shows normal (top) and mutant (underneath) nucleotide sequences. b Proband of family 1 at the age of 2.5 months with inserted Ryle tube for feeding, short neck, short hands and digits, lateral rotation of right upper and lower limbs and medial rotation of left upper and lower limbs due to severe hypotonia. The picture also shows bilateral low inserted thumbs with dorsi-flexion of both feet, no obvious demarcation of large joints with transverse crease on the left knee and ankles and genital hypoplasia. c X-rays (AP view) showing bilateral mid fractures of humeri (upper panel, arrow) and femora (lower panel, arrow). d Pedigree of family 2 and DNA-sequencing chromatograms corresponding to the 5′-end of FXR1 exon-15 of the mother (carrier) and one of the affected siblings showing a single adenine deletion from a run of eight-adenines in the homozygous state in the patient. The father was not available for carrier testing. Only nucleotide sequence of the wt allele is written on the chromatogram of the mother. e–h Representative photomicrographs of H-E staining. Scale bar 60 µm (e), Masson trichrome staining. Scale bar 500 µm (f), ATPase pH4.3 histochemistry. Scale bar 200 µm (g), and TEM. Scale bar 10 µm (h) from a right triceps biopsy of individual II-4 of family 2. Arrows indicate internalized nuclei, fatty infiltration, and areas of Z-streaming and minicores in e, f and h, respectively. Different fibers in TEM images are numbered