An Alu repeat-mediated genomic GCNT2 deletion underlies congenital cataracts and adult i blood group.
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An Alu repeat-mediated genomic GCNT2 deletion underlies congenital cataracts and adult i blood group. / Borck, Guntram; Kakar, Naseebullah; Hoch, Jochen; Friedrich, Katrin; Freudenberg, Jan; Nürnberg, Gudrun; Yilmaz, Rüstem; Daud, Shakeela; Baloch, Dost Muhammad; Nürnberg, Peter; Oldenburg, Johannes; Ahmad, Jamil; Kubisch, Christian.
In: HUM GENET, Vol. 131, No. 2, 2, 2012, p. 209-216.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - An Alu repeat-mediated genomic GCNT2 deletion underlies congenital cataracts and adult i blood group.
AU - Borck, Guntram
AU - Kakar, Naseebullah
AU - Hoch, Jochen
AU - Friedrich, Katrin
AU - Freudenberg, Jan
AU - Nürnberg, Gudrun
AU - Yilmaz, Rüstem
AU - Daud, Shakeela
AU - Baloch, Dost Muhammad
AU - Nürnberg, Peter
AU - Oldenburg, Johannes
AU - Ahmad, Jamil
AU - Kubisch, Christian
PY - 2012
Y1 - 2012
N2 - We performed homozygosity mapping in a consanguineous Pakistani family segregating autosomal-recessive congenital cataracts and identified linkage to a 3.03 Mb locus on chromosome 6p24 containing the GCNT2 gene. GCNT2 encodes glucosaminyl (N-acetyl) transferase 2, an enzyme responsible for the formation of the blood group I antigen. Rare biallelic GCNT2 mutations have been shown to cause the association of congenital cataracts and the adult i blood group, making GCNT2 the prime candidate gene for the observed phenotype. Indeed, we identified a homozygous deletion segregating with cataracts that encompasses exons 1B, 1C, 2 and 3 of GCNT2. Long-range polymerase chain reaction and breakpoint sequencing revealed that affected individuals in this and in a second, apparently unrelated Pakistani family segregating congenital cataracts are homozygous for the same 93 kb deletion. The deletion is flanked by Alu repeats of the AluS family on both sides and microsatellite genotyping suggested that its occurrence in the two families was the product of recurrent Alu-Alu repeat-mediated nonhomologous recombinations or an old founder effect. Subsequently, we showed that cataract-affected individuals in both families have the adult i blood group, whereas unaffected individuals have blood group I as the vast majority of the population. Because the GCNT2 locus is rich in Short INterspersed Elements (SINE repeats) and thus likely prone to genomic rearrangements, microdeletions or microduplications at this locus might cause a larger than currently anticipated fraction of apparently isolated autosomal-recessive cataracts.
AB - We performed homozygosity mapping in a consanguineous Pakistani family segregating autosomal-recessive congenital cataracts and identified linkage to a 3.03 Mb locus on chromosome 6p24 containing the GCNT2 gene. GCNT2 encodes glucosaminyl (N-acetyl) transferase 2, an enzyme responsible for the formation of the blood group I antigen. Rare biallelic GCNT2 mutations have been shown to cause the association of congenital cataracts and the adult i blood group, making GCNT2 the prime candidate gene for the observed phenotype. Indeed, we identified a homozygous deletion segregating with cataracts that encompasses exons 1B, 1C, 2 and 3 of GCNT2. Long-range polymerase chain reaction and breakpoint sequencing revealed that affected individuals in this and in a second, apparently unrelated Pakistani family segregating congenital cataracts are homozygous for the same 93 kb deletion. The deletion is flanked by Alu repeats of the AluS family on both sides and microsatellite genotyping suggested that its occurrence in the two families was the product of recurrent Alu-Alu repeat-mediated nonhomologous recombinations or an old founder effect. Subsequently, we showed that cataract-affected individuals in both families have the adult i blood group, whereas unaffected individuals have blood group I as the vast majority of the population. Because the GCNT2 locus is rich in Short INterspersed Elements (SINE repeats) and thus likely prone to genomic rearrangements, microdeletions or microduplications at this locus might cause a larger than currently anticipated fraction of apparently isolated autosomal-recessive cataracts.
KW - Humans
KW - Male
KW - Female
KW - Base Sequence
KW - Pedigree
KW - Polymorphism, Single Nucleotide
KW - Sequence Analysis, DNA
KW - Consanguinity
KW - Genetic Linkage
KW - Sequence Deletion
KW - Alu Elements
KW - Blood Group Antigens/genetics
KW - Cataract/congenital/genetics
KW - N-Acetylglucosaminyltransferases/genetics
KW - Humans
KW - Male
KW - Female
KW - Base Sequence
KW - Pedigree
KW - Polymorphism, Single Nucleotide
KW - Sequence Analysis, DNA
KW - Consanguinity
KW - Genetic Linkage
KW - Sequence Deletion
KW - Alu Elements
KW - Blood Group Antigens/genetics
KW - Cataract/congenital/genetics
KW - N-Acetylglucosaminyltransferases/genetics
M3 - SCORING: Journal article
VL - 131
SP - 209
EP - 216
JO - HUM GENET
JF - HUM GENET
SN - 0340-6717
IS - 2
M1 - 2
ER -
