PMID- 10487695
OWN - NLM
STAT- MEDLINE
DCOM- 19991006
LR  - 20181201
IS  - 0021-972X (Print)
IS  - 0021-972X (Linking)
VI  - 84
IP  - 9
DP  - 1999 Sep
TI  - A novel mutation in the sodium/iodide symporter gene in the largest family with
      iodide transport defect.
PG  - 3248-53
AB  - We previously reported nine children with an autosomally recessive form of
      congenital hypothyroidism due to an iodide transport defect in a large Hutterite 
      family with extensive consanguinity living in central Canada. Since the original 
      report, we have diagnosed congenital hypothyroidism by newborn TSH screening in 9
      additional children from the family. We performed direct sequencing of the PCR
      products of each NIS (sodium/iodide symporter) gene exon with flanking introns
      amplified from genomic DNA extracted from peripheral blood cells of the patients.
      We identified a novel NIS gene mutation, G395R (Gly395-->Arg; GGA-->AGA), in 10
      patients examined in the present study. All of the parents tested were
      heterozygous for the mutation, suggesting that the patients were homozygous. The 
      mutation was located in the 10th transmembrane helix. Expression experiments by
      transfection of the mutant NIS complimentary DNA into COS-7 cells showed no
      perchlorate-sensitive iodide uptake, confirming that the mutation is the direct
      cause of the iodide transport defect in these patients. A patient who showed an
      intermediate saliva/serum technetium ratio (14.0; normal, > or = 20) and was
      considered to have a partial or less severe defect in the previous report (IX-24)
      did not have a NIS gene mutation. It is now possible to use gene diagnostics of
      this unique NIS mutation to identify patients with congenital hypothyroidism due 
      to an iodide transport defect in this family and to determine the carrier state
      of potential parents for genetic counseling and arranging rapid and early
      diagnosis of their infants.
FAU - Kosugi, S
AU  - Kosugi S
AD  - Department of Laboratory Medicine, Kyoto University School of Medicine, Japan.
      kosugi@kuhp.kyoto-u.ac.jp
FAU - Bhayana, S
AU  - Bhayana S
FAU - Dean, H J
AU  - Dean HJ
LA  - eng
PT  - Case Reports
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Clin Endocrinol Metab
JT  - The Journal of clinical endocrinology and metabolism
JID - 0375362
RN  - 0 (Carrier Proteins)
RN  - 0 (DNA, Complementary)
RN  - 0 (Iodides)
RN  - 0 (Membrane Proteins)
RN  - 0 (Symporters)
RN  - 4XE5NDT4K1 (sodium-iodide symporter)
SB  - AIM
SB  - IM
MH  - Animals
MH  - Biological Transport
MH  - COS Cells
MH  - Carrier Proteins/*genetics
MH  - *Congenital Hypothyroidism
MH  - Consanguinity
MH  - DNA, Complementary
MH  - Female
MH  - Heterozygote
MH  - Homozygote
MH  - Humans
MH  - Hypothyroidism/diagnosis/*genetics
MH  - Infant, Newborn
MH  - Iodides/*metabolism
MH  - Male
MH  - Membrane Proteins/*genetics
MH  - *Mutation
MH  - Neonatal Screening
MH  - Pedigree
MH  - *Symporters
MH  - Transfection
EDAT- 1999/09/16 00:00
MHDA- 1999/09/16 00:01
CRDT- 1999/09/16 00:00
PHST- 1999/09/16 00:00 [pubmed]
PHST- 1999/09/16 00:01 [medline]
PHST- 1999/09/16 00:00 [entrez]
AID - 10.1210/jcem.84.9.5971 [doi]
PST - ppublish
SO  - J Clin Endocrinol Metab. 1999 Sep;84(9):3248-53. doi: 10.1210/jcem.84.9.5971.