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An intronic alteration of the fibroblast growth factor 10 gene causing ALSG-(aplasia of lacrimal and salivary glands) syndrome.

Scheckenbach K, Balz V, Wagenmann M, Hoffmann TK - BMC Med. Genet. (2008)

Bottom Line: The alteration derogates the regular splice acceptor site and leads to the use of a new splice acceptor site 127 bp upstream of exon 3.Furthermore, no diseased member of the family displayed additional abnormalities that are indicative for the clinically overlapping lacrimo-auriculo-dento-digital syndrome (LADD).This family-based approach revealed an intronic variation of the FGF10 gene causing ALSG-syndrome.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Otorhinolaryngology, Heinrich-Heine-University, Düsseldorf, Germany. scheckenbach@med.uni-duesseldorf.de

ABSTRACT

Background: A combined aplasia, hypoplasia or atresia of lacrimal points and salivary glands is rarely diagnosed. Those patients suffer from epiphora, xerostomia and severe dental caries. This phenotype represents the autosomal-dominant aplasia of lacrimal and salivary glands syndrome (ALSG). Recently, aberrations of the Fibroblast Growth Factor 10 (FGF10) gene have been identified to be causative for this disorder.

Methods: We performed a sequence analysis of the FGF10 gene of a patient with ALSG-syndrome and his also affected brother as well as 193 controls. The FGF10 transcript was analyzed using RNA extracted from primary fibroblasts of the patient's mucosa.

Results: We detected a novel heterozygous sequence variation in intron 2 (c.430-1, G > A) causing the ALSG syndrome. The alteration derogates the regular splice acceptor site and leads to the use of a new splice acceptor site 127 bp upstream of exon 3. The aberration was detected in the genomic DNA derived from two affected brothers, but not in 193 control individuals. Furthermore, no diseased member of the family displayed additional abnormalities that are indicative for the clinically overlapping lacrimo-auriculo-dento-digital syndrome (LADD).

Conclusion: This family-based approach revealed an intronic variation of the FGF10 gene causing ALSG-syndrome. Our results expand the mutational and clinical spectrum of the ALSG syndrome.

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Related in: MedlinePlus

a: A heterozygous sequence variation in the terminal nucleotide of intron 2 of the FGF10 gene (g.85478 corresponding to c.430-1, G > A) was detected which alters the consensus motif for splice acceptor site recognition. The upper panel shows a representative electropherogram of a healthy individual. The middle and the lower panel demonstrate the sequence variation in genomic DNA derived from the patient and his brother. The changed nucleotide is marked by an arrow. 2b: Chart showing the exon/intron structure of the FGF10 gene. The characteristic polypyrimidine stretch and the consensus acceptor site are shown. The changed nucleotide is marked by an arrow.
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Figure 2: a: A heterozygous sequence variation in the terminal nucleotide of intron 2 of the FGF10 gene (g.85478 corresponding to c.430-1, G > A) was detected which alters the consensus motif for splice acceptor site recognition. The upper panel shows a representative electropherogram of a healthy individual. The middle and the lower panel demonstrate the sequence variation in genomic DNA derived from the patient and his brother. The changed nucleotide is marked by an arrow. 2b: Chart showing the exon/intron structure of the FGF10 gene. The characteristic polypyrimidine stretch and the consensus acceptor site are shown. The changed nucleotide is marked by an arrow.

Mentions: The recently described interrelation between the ALSG syndrome and alterations in the FGF10 gene prompted us to perform sequence analysis of the entire three exons, the 5'- and 3'-UTRs, and exon flanking sequences of the FGF10 gene in gDNA derived from patient's PBMCs. Five different single nucleotide polymorphisms are described for the FGF10 transcript with variable allele frequencies, located in the 5'-UTR, in the translated part of exon 3 and in the 3'-UTR (1, 1, and 3 polymorphisms, respectively). However, none of these SNPs was found. However, we detected a heterozygous sequence variation in the terminal nucleotide of intron 2 (c.430-1, G > A) altering the consensus motif for splice site recognition (Fig. 2). The aberration was also found in gDNA isolated from PBMCs of the patient's brother who also suffers from ALSG. Moreover, it was not detected in gDNA derived from 386 control chromosomes nor reported in the GeneSnp database or in the Human Gene Mutation database available at and , respectively.


An intronic alteration of the fibroblast growth factor 10 gene causing ALSG-(aplasia of lacrimal and salivary glands) syndrome.

Scheckenbach K, Balz V, Wagenmann M, Hoffmann TK - BMC Med. Genet. (2008)

a: A heterozygous sequence variation in the terminal nucleotide of intron 2 of the FGF10 gene (g.85478 corresponding to c.430-1, G > A) was detected which alters the consensus motif for splice acceptor site recognition. The upper panel shows a representative electropherogram of a healthy individual. The middle and the lower panel demonstrate the sequence variation in genomic DNA derived from the patient and his brother. The changed nucleotide is marked by an arrow. 2b: Chart showing the exon/intron structure of the FGF10 gene. The characteristic polypyrimidine stretch and the consensus acceptor site are shown. The changed nucleotide is marked by an arrow.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2626586&req=5

Figure 2: a: A heterozygous sequence variation in the terminal nucleotide of intron 2 of the FGF10 gene (g.85478 corresponding to c.430-1, G > A) was detected which alters the consensus motif for splice acceptor site recognition. The upper panel shows a representative electropherogram of a healthy individual. The middle and the lower panel demonstrate the sequence variation in genomic DNA derived from the patient and his brother. The changed nucleotide is marked by an arrow. 2b: Chart showing the exon/intron structure of the FGF10 gene. The characteristic polypyrimidine stretch and the consensus acceptor site are shown. The changed nucleotide is marked by an arrow.
Mentions: The recently described interrelation between the ALSG syndrome and alterations in the FGF10 gene prompted us to perform sequence analysis of the entire three exons, the 5'- and 3'-UTRs, and exon flanking sequences of the FGF10 gene in gDNA derived from patient's PBMCs. Five different single nucleotide polymorphisms are described for the FGF10 transcript with variable allele frequencies, located in the 5'-UTR, in the translated part of exon 3 and in the 3'-UTR (1, 1, and 3 polymorphisms, respectively). However, none of these SNPs was found. However, we detected a heterozygous sequence variation in the terminal nucleotide of intron 2 (c.430-1, G > A) altering the consensus motif for splice site recognition (Fig. 2). The aberration was also found in gDNA isolated from PBMCs of the patient's brother who also suffers from ALSG. Moreover, it was not detected in gDNA derived from 386 control chromosomes nor reported in the GeneSnp database or in the Human Gene Mutation database available at and , respectively.

Bottom Line: The alteration derogates the regular splice acceptor site and leads to the use of a new splice acceptor site 127 bp upstream of exon 3.Furthermore, no diseased member of the family displayed additional abnormalities that are indicative for the clinically overlapping lacrimo-auriculo-dento-digital syndrome (LADD).This family-based approach revealed an intronic variation of the FGF10 gene causing ALSG-syndrome.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Otorhinolaryngology, Heinrich-Heine-University, Düsseldorf, Germany. scheckenbach@med.uni-duesseldorf.de

ABSTRACT

Background: A combined aplasia, hypoplasia or atresia of lacrimal points and salivary glands is rarely diagnosed. Those patients suffer from epiphora, xerostomia and severe dental caries. This phenotype represents the autosomal-dominant aplasia of lacrimal and salivary glands syndrome (ALSG). Recently, aberrations of the Fibroblast Growth Factor 10 (FGF10) gene have been identified to be causative for this disorder.

Methods: We performed a sequence analysis of the FGF10 gene of a patient with ALSG-syndrome and his also affected brother as well as 193 controls. The FGF10 transcript was analyzed using RNA extracted from primary fibroblasts of the patient's mucosa.

Results: We detected a novel heterozygous sequence variation in intron 2 (c.430-1, G > A) causing the ALSG syndrome. The alteration derogates the regular splice acceptor site and leads to the use of a new splice acceptor site 127 bp upstream of exon 3. The aberration was detected in the genomic DNA derived from two affected brothers, but not in 193 control individuals. Furthermore, no diseased member of the family displayed additional abnormalities that are indicative for the clinically overlapping lacrimo-auriculo-dento-digital syndrome (LADD).

Conclusion: This family-based approach revealed an intronic variation of the FGF10 gene causing ALSG-syndrome. Our results expand the mutational and clinical spectrum of the ALSG syndrome.

Show MeSH
Related in: MedlinePlus