PMID- 10521295
OWN - NLM
STAT- MEDLINE
DCOM- 19991210
LR  - 20181113
IS  - 0002-9297 (Print)
IS  - 0002-9297 (Linking)
VI  - 65
IP  - 5
DP  - 1999 Nov
TI  - A founder mutation in the GK1 gene is responsible for galactokinase deficiency in
      Roma (Gypsies).
PG  - 1299-307
AB  - Galactokinase deficiency is an inborn error in the first step of galactose
      metabolism. Its major clinical manifestation is the development of cataracts in
      the first weeks of life. It has also been suggested that carriers of the
      deficiency are predisposed to presenile cataracts developing at age 20-50 years. 
      Newborn screening data suggest that the gene frequency is very low worldwide but 
      is higher among the Roma in Europe. Since the cloning of the galactokinase gene
      (GK1) in 1995, only two disease-causing mutations, both confined to single
      families, have been identified. Here we present the results of a study of six
      affected Romani families from Bulgaria, where index patients with galactokinase
      deficiency have been detected by the mass screening. Genetic linkage mapping
      placed the disease locus on 17q, and haplotype analysis revealed a small
      conserved region of homozygosity. Using radiation hybrid mapping, we have shown
      that GK1 is located in this region. The founder Romani mutation identified in
      this study is a single nucleotide substitution in GK1 resulting in the
      replacement of the conserved proline residue at amino acid position 28 with
      threonine (P28T). The P28T carrier rate in this endogamous population is
      approximately 5%, suggesting that the mutation may be an important cause of early
      childhood blindness in countries with a sizeable Roma minority.
FAU - Kalaydjieva, L
AU  - Kalaydjieva L
AD  - Centre for Human Genetics, Edith Cowan University, Joondalup Campus, Perth WA
      6027, Australia. L.Kalaydjieva@cowan.edu.au
FAU - Perez-Lezaun, A
AU  - Perez-Lezaun A
FAU - Angelicheva, D
AU  - Angelicheva D
FAU - Onengut, S
AU  - Onengut S
FAU - Dye, D
AU  - Dye D
FAU - Bosshard, N U
AU  - Bosshard NU
FAU - Jordanova, A
AU  - Jordanova A
FAU - Savov, A
AU  - Savov A
FAU - Yanakiev, P
AU  - Yanakiev P
FAU - Kremensky, I
AU  - Kremensky I
FAU - Radeva, B
AU  - Radeva B
FAU - Hallmayer, J
AU  - Hallmayer J
FAU - Markov, A
AU  - Markov A
FAU - Nedkova, V
AU  - Nedkova V
FAU - Tournev, I
AU  - Tournev I
FAU - Aneva, L
AU  - Aneva L
FAU - Gitzelmann, R
AU  - Gitzelmann R
LA  - eng
SI  - GENBANK/L76927
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Am J Hum Genet
JT  - American journal of human genetics
JID - 0370475
RN  - 0 (DNA Primers)
RN  - EC 2.7.1.6 (Galactokinase)
SB  - IM
MH  - Adolescent
MH  - Amino Acid Sequence
MH  - Bulgaria
MH  - Chromosomes, Human, Pair 17
MH  - DNA Primers
MH  - Female
MH  - Galactokinase/*genetics
MH  - Galactosemias/ethnology/*genetics
MH  - Genetic Testing
MH  - Humans
MH  - Infant, Newborn
MH  - Lod Score
MH  - Male
MH  - Molecular Sequence Data
MH  - Mutation
MH  - Neonatal Screening
MH  - Pedigree
MH  - Physical Chromosome Mapping
MH  - Polymerase Chain Reaction
MH  - Protein Structure, Secondary
MH  - Roma/*genetics
MH  - Romania/ethnology
PMC - PMC1288282
EDAT- 1999/10/16 09:00
MHDA- 2000/03/21 09:00
CRDT- 1999/10/16 09:00
PHST- 1999/10/16 09:00 [pubmed]
PHST- 2000/03/21 09:00 [medline]
PHST- 1999/10/16 09:00 [entrez]
AID - S0002-9297(07)62136-3 [pii]
AID - 10.1086/302611 [doi]
PST - ppublish
SO  - Am J Hum Genet. 1999 Nov;65(5):1299-307. doi: 10.1086/302611.