GM08072

GM08072 LCL from B-Lymphocyte

Description:

MATURITY-ONSET DIABETES OF THE YOUNG, TYPE I; MODY1
HEPATOCYTE NUCLEAR FACTOR 4-ALPHA; HNF4A

Affected:

Yes

Sex:

Female

Age:

27 YR (At Sampling)

Overview

Repository

NIGMS Human Genetic Cell Repository

Subcollection

Heritable Diseases
Maturity-Onset Diabetes of the Young

Class

Other Disorders of Known Biochemistry

Biopsy Source

Peripheral vein

Cell Type

B-Lymphocyte

Tissue Type

Blood

Transformant

Epstein-Barr Virus

Sample Source

LCL from B-Lymphocyte

Race

White

Country of Origin

USA

Family Member

Family History

Relation to Proband

niece

Confirmation

Clinical summary/Case history

Species

Homo sapiens

Common Name

Human

Remarks

Clinically affected with MODY; one impaired and one diabetic glucose tolerance test at age 17, normal tests since then; daughter of GM01246 & GM07973; spouse of GM10406; mother of GM08073, GM11090, & GM11600; donor subject has a C>T substitution at codon 268 in exon 7 of the HNF4A (TCF14) gene that results in a CAG>TAG nonsense mutation [Gln268Ter (Q268X)]; donor subject also has a missense polymorphism of the HNF4A (TCF14) gene: a C>T transition at nucleotide 609 in exon 4 (609C>T) resulting in a threonine to isoleucine change at codon 130 [Thr130Ile (T130I)]; extended pedigree available in PMID:102555.

Characterizations

IDENTIFICATION OF SPECIES OF ORIGIN

Species of Origin Confirmed by Nucleoside Phosphorylase, Glucose-6-Phosphate Dehydrogenase, and Lactate Dehydrogenase Isoenzyme Electrophoresis

GENE MAPPING & DOSAGE STUDIES - Y CHROMOSOME

PCR analysis of DNA from this cell culture gave a negative result with a primer for Yq11, DYS227.

Gene

HNF4A

Chromosomal Location

20q12-q13.1

Allelic Variant 1

600281.0001; MATURITY-ONSET DIABETES OF THE YOUNG, TYPE I; MODY1

Identified Mutation

GLN268TER; In the historic R-W pedigree in which Fajans (1989) defined type 1 maturity-onset diabetes of the young (MODY1; 125850), Yamagata et al. (1996) found a a C-to-T substitution in codon 268 of the TCF14 gene that generated a CAG-to-TAG (Q268X) nonsense mutation. Some subjects in the R-W pedigree had inherited the Q268X mutation but were not yet diabetic; in addition, there were subjects in the pedigree who had noninsulin-dependent diabetes mellitus but did not inherit the Q268X mutation or at-risk haplotype. In one case, NIDDM had been diagnosed at the age of 48 years, and the patient was hyperinsulinemic, indicating that this was probably late-onset NIDDM rather than MODY. The patient had 6 children, 1 of whom also had NIDDM; another child had impaired glucose tolerance, and all had only normal alleles at the TCF14 locus.

Phenotypic Data

Remarks

Publications

Petrovick MS, Boettcher T, Fremont-Smith P, Peragallo C, Ricke DO, Watkins J, Schwoebel E, Analysis of complex DNA mixtures using massively parallel sequencing of SNPs with low minor allele frequencies Forensic science international Genetics46:102234 2019

PubMed ID: 32018060

Herman WH, Fajans SS, Smith MJ, Polonsky KS, Bell GI, Halter JB, Diminished insulin and glucagon secretory responses to arginine in nondiabetic subjects with a mutation in the hepatocyte nuclear factor-4alpha/MODY1 gene. Diabetes46:1749-54 1997

PubMed ID: 9356021

Herman WH, Fajans SS, Ortiz FJ, Smith MJ, Sturis J, Bell GI, Polonsky KS, Halter JB, Abnormal insulin secretion, not insulin resistance, is the genetic or primary defect of MODY in the RW pedigree [published erratum appears in Diabetes 1994 Sep;43(9):1171] Diabetes43:40-6 1994

PubMed ID: 8262315

Ting CN, Burgess DL, Chamberlain JS, Keith TP, Falls K, Meisler MH, Phosphoenolpyruvate carboxykinase (GTP): characterization of the human PCK1 gene and localization distal to MODY on chromosome 20. Genomics16:698-706 1993

PubMed ID: 8325643

Bell GI, Xiang KS, Newman MV, Wu SH, Wright LG, Fajans SS, Spielman RS, Cox NJ, Gene for non-insulin-dependent diabetes mellitus (maturity-onset diabetes of the young subtype) is linked to DNA polymorphism on human chromosome 20q. Proc Natl Acad Sci U S A88:1484-8 1991

PubMed ID: 1899928

Fajans SS, Maturity-onset diabetes of the young (MODY). Diabetes Metab Rev5:579-606 1989

PubMed ID: 2689121

Fajans SS, Cloutier MC, Crowther RL, The Banting Memorial Lecture 1978. Clinical and etiologic heterogeneity of idiopathic diabetes mellitus. Diabetes27:1112-25 1978

PubMed ID: 102555