Format

Send to:

Choose Destination
See comment in PubMed Commons below
J Pediatr. 2009 Dec;155(6):888-892.e1. doi: 10.1016/j.jpeds.2009.06.017. Epub 2009 Jul 29.

Thiamine-responsive megaloblastic anemia: identification of novel compound heterozygotes and mutation update.

Author information

  • 1Division of Hematology and Oncology, Children's Hospital Boston and Harvard Medical School, Boston, MA 02115, USA.

Abstract

OBJECTIVE:

To determine causative mutations and clinical status of 7 previously unreported kindreds with TRMA syndrome, (thiamine-responsive megaloblastic anemia, online Mendelian inheritance in man, no. 249270), a recessive disorder of thiamine transporter Slc19A2.

STUDY DESIGN:

Genomic DNA was purified from blood, and SLC19A2 mutations were characterized by sequencing polymerase chain reaction-amplified coding regions and intron-exon boundaries of all probands. Compound heterozygotes were further analyzed by sequencing parents, or cloning patient genomic DNA, to ascertain that mutations were in trans.

RESULTS:

We detected 9 novel SLC19A2 mutations. Of these, 5 were missense, 3 were nonsense, and 1 was insertion. Five patients from 4 kindreds were compound heterozygotes, a finding not reported previously for this disorder, which has mostly been found in consanguineous kindreds.

CONCLUSION:

SLC19A2 mutation sites in TRMA are heterogeneous; with no regional "hot spots." TRMA can be caused by heterozygous compound mutations; in these cases, the disorder is found in outbred populations. To the extent that heterozygous patients were ascertained at older ages, a plausible explanation is that if one or more allele(s) is not null, partial function might be preserved. Phenotypic variability may lead to underdiagnosis or diagnostic delay, as the average time between the onset of symptoms and diagnosis was 8 years in this cohort.

PMID:
19643445
[PubMed - indexed for MEDLINE]
PMCID:
PMC2858590
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science Icon for PubMed Central
    Loading ...
    Write to the Help Desk