Coincidence of a novel KCNJ11 missense variant R365H with a paternally inherited 6q24 duplication in a patient with transient neonatal diabetes.
OBJECTIVE
Neonatal diabetes is a heterogeneous group of disorders with diabetes manifestation in the first 6 months of life. The most common etiology in permanent neonatal diabetes is mutations of the ATP-sensitive K(+) channel subunits; in transient neonatal diabetes, chromosome 6q24 abnormalities are the most common cause.


METHODS
We report a sporadic case of diabetes without ketoacidosis diagnosed on the fourth day of life.


RESULTS
Analysis of the KCNJ11 gene found a novel R365H mutation in the proband and her unaffected father. The functional analysis did not support pathogenicity of this variant. When the patient's diabetes remitted in the seventh month of life, the 6q24 region was analyzed and a paternally inherited duplication was identified.


CONCLUSIONS
Our case reports a coincidental novel KCNJ11 variant in a patient with transient neonatal diabetes due to a 6q24 duplication, illustrating the difficulty in testing neonates before the clinical course of neonatal diabetes is known.
Staník
Juraj
J
DIABGENE and Diabetes Laboratory, Institute of Experimental Endocrinology, Slovak Academy of Sciences, Bratislava, Slovakia.
Lethby
Mark
M
Flanagan
Sarah E
SE
Gasperíková
Daniela
D
Milosovicová
Beata
B
Lever
Margaret
M
Bullman
Hilary
H
Zubcevic
Lejla
L
Hattersley
Andrew T
AT
Ellard
Sian
S
Ashcroft
Frances M
FM
Klimes
Iwar
I
D001724:Birth Weight; D002096:C-Peptide / Q000097:blood; D002896:Chromosomes, Human, Pair 6; D003920:Diabetes Mellitus / Q000188:drug therapy / Q000235:genetics*; D005260:Female; D020440:Gene Duplication; D014644:Genetic Variation; D006801:Humans; D007230:Infant, Low Birth Weight; D007231:Infant, Newborn; D007328:Insulin / Q000097:blood / Q000627:therapeutic use; D008297:Male; D020125:Mutation, Missense; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics*; D000099161:Kcnj11 Channel
D002096:C-Peptide; D007328:Insulin; D024661:Potassium Channels, Inwardly Rectifying; D000099161:Kcnj11 Channel