Genotype-phenotype associations in children with congenital hyperinsulinism

Maria Melikyan, Klaus Brusgaard, Elena Petraykina, Igor Volkov, Yulia Averyanova, Maria Kareva, Valentina Peterkova, larisa Gurevich, Henrik Thybo Christesen

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Congenital hyperinsulinism (CHI) is a heterogeneous disease in terms of clinical presentation, genetics and histology. Mutations in eight genes
are known to be a cause of CHI, of which ABCC8, KCNJ11 and GCK are among the most common.
We investigated genotype-phenotype associations in a cohort of Russian patients with CHI by clinical characterization and bidirectional direct
sequencing of the ABCC8, KCNJ11 and GCK genes.
33 children were identified, of which 18 (54,5%) responded to the medical therapy (diazoxide and/or somatostatine) and 15 (45,5%) were resistant and
underwent subtotal or partial pancreatectomy. Histological examination of the removed pancreatic tissue revealed 7 (47%) diffuse, 7(47%) focal, and 1
(6%) atypical form of CHI. Among medically responsive, 4 children (22%) spontaneously recovered during one year after the diagnosis. Mutations were
found in 12 patients (36%); 4 (22%) of the medical responsive and 8 (53%) of the medical resistant patients, Table 1. Ten (83%) of the mutations were
found in the KATP-channel genes ABCC8 and KCNJ11. The same heterozygous, novel ABCC8 mutation Q444H was seen in 4 unrelated families,
causing medically resistant focal form in 3 patients and diazoxide responsive form in 1. GCK mutations were medical responsive, and resistant,
respectively. There were no mutation carriers among children with spontaneously recovery.
Table 1. Gentotype-phenotype correlation in patients with mutations detected
Number of patients 8 2 2
Mutations found in medically responsive cases R74L hetz
Q444H hetz A96T homoz V91L hetz, de novo
Mutations found in medically resistant cases of focal forms
Q444H hetz, paternal
Q444H hetz
Q444H hetz
R841P hetz, paternal
R136AfsX5 hetz, de novo -
Mutations found in medically resistant cases of diffuse forms R998X hetz
delF1387 hetz, de novo - Y241C hetz
Hetz – heterozygous; homoz – homozygous
Conclusion: A genetic cause was detected in 23%, and 53%, of children with mild, and severe CHI, respectively, in Russia. The ABCC8 mutation
Q444H was prevalent and found in both medical responsive and resistant patient. Further genetic investigations are pending.
Original languageEnglish
Publication dateSep 2011
Number of pages1
Publication statusPublished - Sep 2011
Event50th ESPE Meeting - Glasgow, United Kingdom
Duration: 25. Sep 2011 → …


Conference50th ESPE Meeting
Country/TerritoryUnited Kingdom
Period25/09/2011 → …

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