PMC3237658_01
A: Family pedigree. Circles represent females and squares represent males. Dark gray-filled symbols indicate CHI-affected heterozygotes, the light gray-filled symbol represents heterozygotes with mild phenotype, and symbols with dots represent unaffected heterozygotes. Diamonds represent several healthy male and female siblings. Square with the diagonal slash represents a deceased male. Roman numerals indicate the generation, Arabic numerals indicate the specific individual, and the proband is indicated with an arrow. B: A schematic diagram of the ABCC8 gene. Exons are depicted as boxes and are not drawn to scale. Arrow represents the transcription start site. Exon 12 contains the MaeII restriction polymorphic site. Exon 37 contains the in-frame insertion mutation (1508AS) of six bp (CGGCTT). L1 and R1 indicate the locations of the primers used for bisulfite methylation analysis of the gene promoter region. L2 and R2 indicate the location of the primers used to identify the MaeII polymorphic site and L3 and R3 that of the primers used to identify the mutation. C: Sequencing results showing part of exon 37 of the ABCC8 gene demonstrating the in-frame insertion mutation of six nucleotides (CGGCTT; 1508AS) in the proband's DNA. D: A schematic diagram of the imprinted genes located in the chromosome 11p15.5 region. Maternally expressed genes CDKN1C, H19, and KCNQ1 are depicted as gray boxes. The paternally expressed gene (Igf2) is depicted as a black box. Biallelically expressed genes KCNJ11 and ABCC8 are depicted as white boxes. The ICR is located at the KCNQ1 (LIT1) gene sequence. L4 and R4 are primers for the ICR. (A high-quality color representation of this figure is available in the online issue.)
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F1
Arabic numerals indicating the specific individual]) (Fig. 1A), born large for gestational age (4.8 kg) to nonconsanguineous Palestinian parents, developed severe hyperinsulinemic (10.1 mU/L) hypoglycemia (20 mg/dL) without ketonuria (ammonia and lactate were normal). Because a heterozygous six-base pair (bp) in-frame insertion mutation in ABCC8 exon 37 was found in the cousin (II-2) and her unaffected haploidentical brother (II-3) but not in their mother (I-1) (Fig. 1B and C), it was thought that patient II-2 had focal CHI as a result of paternal uniparental disomy or paternal mutation and LOH.