Fig. 1

Pedigrees, genetic findings and clinical features of three families with mutations in TRIM32. a Pedigree of Spanish family (family A) having the missense c.1771G > A (p.V591 M) mutation that segregates with the disease: homozygous only in affected patients. Pedigree of Australian family (family B) presenting the missense c.650A > G (p.N217S) mutation in combination with the frameshift c.1701_1703del (p.F568del) mutation that segregate with the disease: compound-heterozygosity only in affected patients. Pedigree of Spanish family (family C) possessing the homozygous frameshift mutation c.115_116insT (p.C39LfsX17) that segregates with the disease: homozygous only in affected patients. In the non-affected siblings (red symbols) of the three pedigrees we found only one or no mutated alleles. Circles denote female members and squares male members. Double line denotes a consanguineous marriage. Solid black symbols denote affected patients. b. Chromatograms display the homozygous missense c.650A > G (p.N217S), heterozygous missense c.650A > G (p.N217S), heterozygous frameshift c.1701_1703del (p.F568del) and homozygous frameshift mutations in the TRIM32 gene. Arrows indicate the location of the base change. The TRIM32 functional domains RING finger domain, B-box type 1 domain, coiled-coil region, and six NHL repeats are represented in the scheme, where arrows indicate the novel mutations location in the TRIM32 protein structure. c. Distal muscle involvement led to distal atrophy and ankle contractions. Patient II.3 from Family C showed mild paravertebral muscle atrophy with no scapular winging. d. Muscle MRI T1-weighted axial images at gluteus, thigh and calf levels showed different patterns of muscle involvement in the three families