Identification of 14 novel CTNS mutations and characterization of seven splice site mutations associated with cystinosis.
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Identification of 14 novel CTNS mutations and characterization of seven splice site mutations associated with cystinosis. / Kalatzis, Vasiliki; Cohen-Solal, Lola; Cordier, Béatrice; Frishberg, Yaacov; Kemper, Markus J.; Nuutinen, E Matti; Legrand, Eric; Cochat, Pierre; Antignac, Corinne.
in: HUM MUTAT, Jahrgang 20, Nr. 6, 6, 2002, S. 439-446.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - Identification of 14 novel CTNS mutations and characterization of seven splice site mutations associated with cystinosis.
AU - Kalatzis, Vasiliki
AU - Cohen-Solal, Lola
AU - Cordier, Béatrice
AU - Frishberg, Yaacov
AU - Kemper, Markus J.
AU - Nuutinen, E Matti
AU - Legrand, Eric
AU - Cochat, Pierre
AU - Antignac, Corinne
PY - 2002
Y1 - 2002
N2 - Cystinosis is an autosomal recessive disorder characterized by intra-lysosomal accumulation of cystine. Three disease forms exist, infantile, juvenile, and ocular nonnephropathic cystinosis, delineated on the basis of severity of symptoms and age of onset. Mutations in the causative gene, CTNS, which encodes cystinosin, the seven transmembrane domain lysosomal cystine transporter, have been identified in all forms confirming their allelic status. By screening for mutations in the CTNS exons and promotor region, we report 14 novel mutations associated with cystinosis: 11 underlying infantile cystinosis, two juvenile cystinosis, and one associated with an atypical form of the disease. These mutations, all situated in the exons or immediately flanking intronic sequences, comprise in-frame insertions and deletions, as well as missense, nonsense, and putative splice-site mutations. Furthermore, we confirmed the putative splice-site mutations we have reported to date (five novel and two previously reported) by isolation of RNA from the affected carriers and characterization of the resultant transcripts using RT-PCR. Since the cloning of CTNS, we have screened for mutations in 108 affected individuals, which has resulted in a high mutation detection rate of 95.8%. Interestingly, the few undetectable mono- or bi-allelic mutations segregated mostly in the noninfantile forms, suggesting that these individuals carry mutations either in the introns or in unidentified regulatory sequences.
AB - Cystinosis is an autosomal recessive disorder characterized by intra-lysosomal accumulation of cystine. Three disease forms exist, infantile, juvenile, and ocular nonnephropathic cystinosis, delineated on the basis of severity of symptoms and age of onset. Mutations in the causative gene, CTNS, which encodes cystinosin, the seven transmembrane domain lysosomal cystine transporter, have been identified in all forms confirming their allelic status. By screening for mutations in the CTNS exons and promotor region, we report 14 novel mutations associated with cystinosis: 11 underlying infantile cystinosis, two juvenile cystinosis, and one associated with an atypical form of the disease. These mutations, all situated in the exons or immediately flanking intronic sequences, comprise in-frame insertions and deletions, as well as missense, nonsense, and putative splice-site mutations. Furthermore, we confirmed the putative splice-site mutations we have reported to date (five novel and two previously reported) by isolation of RNA from the affected carriers and characterization of the resultant transcripts using RT-PCR. Since the cloning of CTNS, we have screened for mutations in 108 affected individuals, which has resulted in a high mutation detection rate of 95.8%. Interestingly, the few undetectable mono- or bi-allelic mutations segregated mostly in the noninfantile forms, suggesting that these individuals carry mutations either in the introns or in unidentified regulatory sequences.
KW - Adult
KW - Humans
KW - Male
KW - Female
KW - Adolescent
KW - Child
KW - DNA Mutational Analysis
KW - Reverse Transcriptase Polymerase Chain Reaction
KW - Family Health
KW - Heterozygote
KW - Membrane Proteins/genetics
KW - Alternative Splicing/genetics
KW - Amino Acid Transport Systems, Neutral
KW - Cystinosis/genetics/pathology
KW - DNA/chemistry/genetics
KW - Genes/genetics
KW - Glycoproteins
KW - Membrane Transport Proteins
KW - RNA/genetics/metabolism
KW - Adult
KW - Humans
KW - Male
KW - Female
KW - Adolescent
KW - Child
KW - DNA Mutational Analysis
KW - Reverse Transcriptase Polymerase Chain Reaction
KW - Family Health
KW - Heterozygote
KW - Membrane Proteins/genetics
KW - Alternative Splicing/genetics
KW - Amino Acid Transport Systems, Neutral
KW - Cystinosis/genetics/pathology
KW - DNA/chemistry/genetics
KW - Genes/genetics
KW - Glycoproteins
KW - Membrane Transport Proteins
KW - RNA/genetics/metabolism
M3 - SCORING: Journal article
VL - 20
SP - 439
EP - 446
JO - HUM MUTAT
JF - HUM MUTAT
SN - 1059-7794
IS - 6
M1 - 6
ER -
