Rhabdomyolysis and Metabolic Myopathy
Gene: KCNJ11
Single consanguineous family reported with congenital hyperinsulinism and rhabdomyolysis
Sources: LiteratureCreated: 29 May 2020, 4:44 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Hyperinsulinemic hypoglycemia, familial, 2 MIM#601820
Congenital hyperinsulinism (HI) variants are generally reported in heterozygous patients where they also carry a somatic 2nd hit, or have isodisomy of the paternal allele (focal HI), or in bilallelic patients (diffuse HI). This condition can be dominant (but rarely), where patients with these missense are diazoxide-responsive. Patients with recessively inherited variants are diazoxide-unresponsive (OMIM, PMID:11395395, PMID: 23275527, PMID: 23345197).
Genotype-phenotype correlation:
Permanent neonatal diabetes – GOF (OMIM)
Permanent neonatal diabetes + other features – GOF (OMIM)
Congenital hyperinsulinism – LOF (PMID:18250167).
PTCs - LOF
Missense - Loss and gain of function
LOF – cause reduce channel expression, channel activity and increase current decay (PMID:18250167)
GOF - impair ATP-based sensitivity, more open state channel (OMIM)
Mutations generally occur on the paternal allele (PMID: 23345197).Created: 15 Apr 2020, 3:29 a.m. | Last Modified: 15 Apr 2020, 3:29 a.m.
Panel Version: 0.2280
Congenital hyperinsulinism (HI) variants are generally reported in heterozygous patients where they also carry a somatic 2nd hit, or have isodisomy of the paternal allele (focal HI), or in bilallelic patients (diffuse HI). This condition can be dominant (but rarely), where patients with these missense are diazoxide-responsive. Patients with recessively inherited variants are diazoxide-unresponsive (OMIM, PMID:11395395, PMID: 23275527, PMID: 23345197).
Genotype-phenotype correlation:
Permanent neonatal diabetes – GOF (OMIM)
Permanent neonatal diabetes + other features – GOF (OMIM)
Congenital hyperinsulinism – LOF (PMID:18250167).
PTCs - LOF
Missense - Loss and gain of function
LOF – cause reduce channel expression, channel activity and increase current decay (PMID:18250167)
GOF - impair ATP-based sensitivity, more open state channel (OMIM)
Mutations generally occur on the paternal allele (PMID: 23345197).Created: 15 Apr 2020, 3:29 a.m. | Last Modified: 15 Apr 2020, 3:29 a.m.
Panel Version: 0.2280
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes
{Diabetes mellitus, type 2, susceptibility to} 125853; Diabetes mellitus, transient neonatal, 3 610582; Diabetes, permanent neonatal, with or without neurologic features 606176; Hyperinsulinemic hypoglycemia, familial, 2 601820; Maturity-onset diabetes of the young, type 13 616329 AD
Publications
Mode of pathogenicity
Other
Gene: kcnj11 has been classified as Red List (Low Evidence).
gene: KCNJ11 was added gene: KCNJ11 was added to Rhabdomyolysis RMH. Sources: Literature Mode of inheritance for gene: KCNJ11 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: KCNJ11 were set to Hyperinsulinemic hypoglycemia, familial, 2 MIM#601820 Review for gene: KCNJ11 was set to RED