PMID- 10206679
OWN - NLM
STAT- MEDLINE
DCOM- 19990412
LR  - 20131121
IS  - 1059-7794 (Print)
IS  - 1059-7794 (Linking)
VI  - 11
IP  - 5
DP  - 1998
TI  - Novel allele of the insulin receptor substrate-1 bearing two non-conservative
      amino acid substitutions in a patient with noninsulin-dependent diabetes
      mellitus. Mutations in brief no. 130. Online.
PG  - 411
AB  - We analyzed by SSCP the complete IRS-1 coding sequence in NIDDM patient #25 D.
      Unique conformers corresponding to a Ser to Tyr substitution at codon 1043
      (S1043Y), and to a Cys to Tyr substitution at codon 1095 (C1095Y) were detected
      in this patient. The results of sequential digestion with restriction enzymes
      indicated that the novel sequence variants segregate on the same allele.
      Relatives of patient #25 D were not available for study, to confirm segregation
      of the novel allele with NIDDM in the family. Several lines of evidence suggest
      that the non-conservative amino acid substitutions detected in NIDDM patient #25 
      D have the potential to affect IRS-1 functions and could play a pathogenic role
      in this patient. Both S1043Y and C1095Y occur in a highly conserved sequence from
      human skeletal muscle, human hepatoma, mouse, and rat IRS-1. Protein subsequence 
      analysis revealed that the S1043Y substitution abolishes a consensus sequence for
      glycogen synthase kinase 3 phosphorylation. Furthermore, S1043Y and C1095Y are
      not common IRS-1 polymorphisms as they were detected only in 1/136 choromosomes
      from NIDDM patients (allele frequency in NIDDM patients = 0.0007) and in 0/120
      chromosomes from control subjects.
FAU - Mammarella, S
AU  - Mammarella S
AD  - Istituto di Patologia Umana e Medicina Sociale, Universita "Gabriele D'Annunzio" 
      Via dei Vestini 1, 66013 Chieti, Italy.
FAU - Creati, B
AU  - Creati B
FAU - Esposito, D L
AU  - Esposito DL
FAU - Arcuri, P
AU  - Arcuri P
FAU - Della Loggia, F
AU  - Della Loggia F
FAU - Capani, F
AU  - Capani F
FAU - Mariani-Costantini, R
AU  - Mariani-Costantini R
FAU - Caramia, F G
AU  - Caramia FG
FAU - Battista, P
AU  - Battista P
FAU - Cama, A
AU  - Cama A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Hum Mutat
JT  - Human mutation
JID - 9215429
RN  - 0 (IRS1 protein, human)
RN  - 0 (Insulin Receptor Substrate Proteins)
RN  - 0 (Irs1 protein, mouse)
RN  - 0 (Irs1 protein, rat)
RN  - 0 (Phosphoproteins)
RN  - 42HK56048U (Tyrosine)
RN  - 452VLY9402 (Serine)
RN  - EC 2.7.10.1 (Receptor, Insulin)
SB  - IM
MH  - *Alleles
MH  - Amino Acid Substitution/*genetics
MH  - Diabetes Mellitus, Type 2/*genetics
MH  - Humans
MH  - Insulin Receptor Substrate Proteins
MH  - *Phosphoproteins
MH  - Receptor, Insulin/*genetics
MH  - Serine/genetics
MH  - Tyrosine/genetics
EDAT- 1999/04/17 02:16
MHDA- 2000/06/22 10:00
CRDT- 1999/04/17 02:16
PHST- 1999/04/17 02:16 [pubmed]
PHST- 2000/06/22 10:00 [medline]
PHST- 1999/04/17 02:16 [entrez]
AID - 10.1002/(SICI)1098-1004(1998)11:5<411::AID-HUMU11>3.0.CO;2-2 [pii]
AID - 10.1002/(SICI)1098-1004(1998)11:5<411::AID-HUMU11>3.0.CO;2-2 [doi]
PST - ppublish
SO  - Hum Mutat. 1998;11(5):411. doi:
      10.1002/(SICI)1098-1004(1998)11:5<411::AID-HUMU11>3.0.CO;2-2.