case_images: PMC3111034_01
case_images: PMC3111034_02
case_images: PMC3111034_03
case_images: PMC3111034_04
case_images: PMC3111034_05
case_images: PMC3111034_06
case_images: PMC3111034_07
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case_images: PMC3111034_09
case_images: ACADM mutations detected by sequence analysis. Compound heterozygote consisting of a known mutation and a novel mutation in Patient 1. The known maternally-derived allele was a 4-bp deletion at position 449 to 452 in exon 6, altering codon 153 from a proline to a termination codon (p.Thr150ArgfsX4). The novel mutant allele originated from the patient's father and was a T to G transition at position 461 in exon 6, resulting in a leucine to tryptophan change at codon 154 (p.L154W).
case_images: kjlm-31-54-g001.jpg
case_images: PMC3111034_09_kjlm-31-54-g001.jpg
case_images: F1
case_images: In Patient 1, sequence analysis of the ACADM gene revealed a known mutation, c.449_452delCTGA (p.Thr150-ArgfsX4), in exon 6 and a previously unrecognized mutation in the same exon, a T to G transversion at position 461 that would alter a leucine to tryptophan at amino acid position 154 (p.L154W) (Fig. 1).
case_images: Diagram of protein structure near the c.461T>G (p.L154W) mutation. (A) Leu154 lies on the loop between the N-terminal alpha domain and beta domain, shown in sky blue. (B) The novel Leu154Trp mutation produces side-chain clash with Glu152 (dotted pink line). Hydrogen bonds are shown by the dotted green lines.
case_images: kjlm-31-54-g002.jpg
case_images: PMC3111034_09_kjlm-31-54-g002.jpg
case_images: F2
case_images: Using the SWISS-MODEL and Swiss-Pdb Viewer, the protein structure was analyzed: the novel mutation was predicted to cause no significant structural destruction, but it produced a side-chain clash that could result in backbone shifts in order to avoid clashes between amino acid side chains and its local backbone (Fig. 2).
case_images: PMC3111034_10