Elevated serum gastrin levels in Jervell and Lange-Nielsen syndrome: a marker of severe KCNQ1 dysfunction?
BACKGROUND
The potassium channel I(Ks), which is encoded by the KCNQ1 gene, is expressed in organ systems including the inner ear, kidneys, lungs, intestine, and stomach in addition to the heart. Increasing evidence indicates that I(Ks) in the stomach plays an essential role in enabling gastric acid production. It is not known whether gastric acid production is disordered in patients with long QT type 1. Serum gastrin levels become elevated in subjects with disordered gastric acid production.


OBJECTIVE
The purpose of this study was to evaluate serum gastrin levels, as a surrogate for impaired gastric acid secretion, in patients with KCNQ1 mutations, and to see if gastrin levels correlate with severity of cardiac disease.


METHODS
Fasting serum gastrin levels were measured using a standardized immunometric technique in an index case and 12 subjects with known KCNQ1 mutations.


RESULTS
An adult female with Jervell and Lange-Nielsen syndrome (JLNS; with KCNQ1 nonsense mutations p.Arg518X and p.Arg190AlafsX95 ) presented with multiple gastric carcinoid tumors and grossly elevated serum gastrin levels (943-1,570 pmol/L; normal 6-55 pmol/L) and absent acid secretion. Gastrin levels in two girls with JLNS, unrelated to the index case (missense mutations p.Leu266Pro and Gly269Ser), also were high (305 and 229 pmol/L). Gastrin levels were normal in 10 KCNQ1 heterozygous single mutation carriers, even in those with severe long QT syndrome, including three heterozygous family members of the JLNS subjects.


CONCLUSIONS
JLNS may be associated with elevated gastrin levels, impaired acid secretion, and risk of gastric carcinoid tumors. Among KCNQ1 single mutation carriers, gastrin levels were normal and did not appear to be linked to the severity of clinical expression of long QT syndrome.
Green Lane Paediatric and Congenital Cardiac Services, Starship Children's Hospital, Auckland, New Zealand.
Kathryn S
KS
Rice
Graeme
G
Dickson
Mark
M
Lane
Jackie
J
Crawford
Seo-Kyung
SK
Chung
Mark I
MI
Rees
Andrew N
AN
Shelling
Donald R
DR
Love
Jonathan R
JR
Skinner
D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D002648:Child; D002675:Child, Preschool; D004247:DNA / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D005500:Follow-Up Studies; D005755:Gastrins / Q000097:blood*; D006579:Heterozygote; D006801:Humans; D029593:Jervell-Lange Nielsen Syndrome / Q000097:blood* / Q000235:genetics; D051657:KCNQ1 Potassium Channel / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D012720:Severity of Illness Index; D055815:Young Adult
D015415:Biomarkers; D005755:Gastrins; D051657:KCNQ1 Potassium Channel; D004247:DNA