PMC6311306_01
(a) Pedigree of the described Family 1. Parents (III: 1 and III: 2) of the affected individuals (IV: 1, IV: 2 and IV: 3) are first degree relatives. Family 2 Parents (III: 1 and III: 2) of the affected individuals (IV: 1) are first degree relatives. Filled boxes indicate individuals affected by hereditary sensory neuropathy and open boxes indicate phenotypically normal individuals. Homozygous mutant genotype (-/-), heterozygous carrier (+/-), and homozygous wild-type genotype (+/+) were observed. (b) MRI of the foot for the affected individual IV: 1 from Family 1. Note the marked deformity in the toe with metatarsal bone and scar tissue formation. (c) Sanger sequencing analysis of the FAM134B gene (NM_ 001034850) identified a homozygous variant (c.926C>G, p.S309*) in the affected individual (upper panel), homozygous wild type in the normal control (middle panel) and heterozygous in the carrier mother (lower panel). (d) Quantitative real time PCR of FAM134B mRNA for patient IV: 1 from family 1 and his normal sibling IV: 2 showing significant reduction of the transcript level. The experiment was performed in quadruplicate; error bars represent standard error of the mean while the relative expression of FAM134B in controls is set to one and data are normalized to GAPDH mRNA.
CRIG2018-9468049.001.jpg
PMC6311306_01_CRIG2018-9468049.001.jpg
fig1
Family 2: A 15-year-old boy (F2: IV: 1) presented with a history of frequent falls, unsteadiness, and pain insensitivity from an early age of 4 years [Figure 1(a)]. Due to similar phenotype, the index case (IV: 1) and parents from family 2 were also Sanger sequenced for WES-identified variant, which fully segregated with disease phenotype in both families [Figures 1(a) and 1(c)]. Real Time PCR 7500 Fast system. Real time quantification of FAM134B mRNA in the index patient (IV: 1) of family 1 indicated a 4-fold reduction in FAM134B mRNA expression compared to the normal sibling [Figure 1(d)].