A founder variant in the RYR1 gene is associated with hyperCKemia , myalgia and muscle cramps

Figures

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  FIGURE 1. Seventeen individuals with the RYR1 p.Leu2286Val sharing a common haplotype. (a) Pedigrees of the seven families with p.Leu2286Val RYR1 (NM_000540.3:c.6856C>G). Arrows indicate index cases in each family. In families 5, 6 and 7, an in trans RYR1 variant with the p.Leu2286Val was detected (c.3619G>A, p.Val1207Met in 5.III.1, c.6359T>C, p.Met2120Thr in 6.II.1 and c.917C>T, p.Ala306Val in 7.I.2). (b) The genotype of index cases and available relatives of six selected SNPs spanning 147.8 kb. p.Leu2286Val‐associated haplotype is highlighted in yellow.

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  FIGURE 2. MRI patterns in RYR1 p.Leu2286Val patients. (a) Latissimus dorsi was mildly affected in patients 2.II.1 and 4.I.1 (white arrow). Paravertebral muscles were also involved in patient 2.II.1 (asterisk). (b) Glutei minimum involvement (white arrow), as well as iliacus hypertrophy (asterisk), were present in patients 1.II.4, 3.II.1 and 4.I.1. (c) In the thighs, the posterior compartment was more affected than the anterior, especially sartorius, adductor magnus and biceps femoris. Thigh hypertrophy was present in 1.II.4, 3.II.1 and 2.II.1. (d) In the legs, medial gastrocnemius (white arrows) was affected in patients 1.II.4, 2.II.1 and 4.I.1; soleus in patient 2.II.1 (asterisk) and tibialis anterior in patient 4.I.1.

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  FIGURE 3. Histological studies from muscle biopsies of patients 1.II.4 and 3.II.1. (a) Muscle biopsy from patient 1.II.4 showed variable‐size fibres with central nuclei and ring fibres (hematoxylin and eosin not shown). (b) Muscle biopsy of patient 3.II.1 showed central nuclei in a few fibres.