PMC5415723_01
Family pedigree and DNA sequence chromatograms of family members (a) Family pedigree and mutation analysis for exon 4 of MMAA (b) A DNA sequence chromatogram of the family members (B1) DNA sequence chromatogram of the affected daughter (4 years old) with the homozygous c.674delA mutation (B2) DNA sequence chromatogram of the affected son (1.5 years old) with the homozygous c.674delA mutation (B3) DNA sequence chromatogram of the father with the heterozygous c.674delA mutation (B4) DNA sequence chromatogram of the mother with the heterozygous c.674delA mutation (B5) DNA sequence chromatogram of the unaffected son with the heterozygous c.674delA mutation
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PMC5415723_01_11658_2016_5_Fig1_HTML.jpg
Fig1
The family pedigree is shown in Fig. 1a. The family pedigree and sequence chromatograms for exon 4 of MMAA from the five family members are shown in Fig. 1.
cDNA sequence chromatogram and expression analysis of beta-actin and MMAA gene. a cDNA sequence chromatogram of MMAA from the affected daughter and the corresponding amino acid sequence, premature TAA stop codon 12 amino acids downstream of the methionine produced by the frame shift (green) (b) beta-actin (size: 113 bp): Lanes 1: 100 bp marker, 2: cDNA from the affected daughter with the c.674delA mutation, 3: cDNA from a normal control, 4: negative control. c MMAA, exon 4, size: 508 bp):Lanes 1: 1 kbp marker, 2: cDNA from the affected daughter with the c.674delA mutation, 3: cDNA from a normal control, 4: negative control
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PMC5415723_01_11658_2016_5_Fig2_HTML.jpg
Fig2
The mRNA expression analysis and sequencing chromatogram of expression analysis are shown in Fig. 2.
Whole view of the normal protein MMAA by the use of 2www structure (above left); close view of the normal protein MMAA (above right); whole view of the novel mutated MMAA protein (p.N225M) by the use of 2www structure (below left); close view of the novel mutated protein MMAA (below right). Red circles in pictures show low complexity regions
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PMC5415723_01_11658_2016_5_Fig3_HTML.jpg
Fig3
As discussed above and shown in Fig. 3, the novel mutation (p.N225M) is the underlying cause of a big frame shift and the loss of a large part of the deduced novel protein due to the early truncation which results in conformational instability.