PMC6383084_01
Pedigree of the family described in this study. Subjects II.1 GC and II.3 TS
represent the index cases on whom whole exome sequencing was performed.
Subjects I.1 MS and II.5 SS respectively represent the father and a third
sibling. The c.872dupC mutation was confirmed by Sanger sequencing in these
four patients, all with varying clinical presentations of diabetes. HNF1alpha
indicates hepatocyte nuclear factor 1alpha.
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PMC6383084_01_10.1177_1179547619831034-fig1.jpg
fig1-1179547619831034
An overview of the pedigree of this family is shown in Figure 1.
(A) Excerpt of whole exome sequencing from proband II.3 TS visualised using
Integrative Genomics Viewer. The position of the pathogenic frameshift at
121432116 (hg19) in HNF1A is indicated by the vertical I
bars. The mismatched base shown (C) indicates the common neighbouring single
nucleotide variant, rs56348580 at position 121432117. The latter is a benign
synonymous substitution c.864G>C (p.Gly288=) that was present in the
homozygous form in proband II.3 TS and in the heterozygous state in the
other two siblings and their father. (B) Sanger sequencing trace showing the
control sequence (top) and the duplication at position 121432116 in probands
II.1 GC, II.3 TS, and I.1 MS. The position of the duplication within the
polyC tract in exon4 is indicated by the grey bar. The red asterisk in the
trace from proband II.3 TS indicates the neighbouring benign G to C variant
(rs56348580) at position 121432117, which overlaps with the peak of the C
nucleotide insC mutation at 121432116. Downstream of the polyC tract, the
superimposed traces caused by chromatogram shift due to the heterozygous
duplication can be observed in the bottom two traces but not in the control
sequence.
10.1177_1179547619831034-fig2.jpg
PMC6383084_01_10.1177_1179547619831034-fig2.jpg
fig2-1179547619831034
A duplication of a C nucleotide at position 121432116 of the GRCh37/hg19 assembly was identified, corresponding to the polyC tract within exon 4 of the HNF1A gene (RefSeq accession number NM_000545.6: c.872dup) (Figure 2).