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Alstrom syndrome (OMIM 203800): a case report and literature review.

Joy T, Cao H, Black G, Malik R, Charlton-Menys V, Hegele RA, Durrington PN - Orphanet J Rare Dis (2007)

Bottom Line: Mutations in the ALMS1 gene have been found to be causative for AS with a total of 79 disease-causing mutations having been described.Examination of her family revealed that her phenotypically unaffected mother and younger sister also had heterozygous mutations in the ALMS1 gene.Two novel mutations in the ALMS1 gene causative for AS have been reported here, thereby increasing the number of reported mutations to 81 and providing a wider basis for mutational screening among affected individuals.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Vascular Biology and Medicine, Robarts Research Institute and Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada. tjoy@uwo.ca

ABSTRACT

Background: Alstrom syndrome (AS) is a rare autosomal recessive disease characterized by multiorgan dysfunction. The key features are childhood obesity, blindness due to congenital retinal dystrophy, and sensorineural hearing loss. Associated endocrinologic features include hyperinsulinemia, early-onset type 2 diabetes, and hypertriglyceridemia. Thus, AS shares several features with the common metabolic syndrome, namely obesity, hyperinsulinemia, and hypertriglyceridemia. Mutations in the ALMS1 gene have been found to be causative for AS with a total of 79 disease-causing mutations having been described.

Case presentation: We describe the case of a 27-year old female from an English (Caucasian) kindred. She had been initially referred for hypertriglyceridemia, but demonstrated other features suggestive of AS, including blindness, obesity, type 2 diabetes, renal dysfunction, and hypertension. DNA analysis revealed that she is a compound heterozygote with two novel mutations in the ALMS1 gene - H3882Y and V424I. Examination of her family revealed that her phenotypically unaffected mother and younger sister also had heterozygous mutations in the ALMS1 gene. In addition to presenting these novel molecular findings for AS, we review the clinical and genetic features of AS in the context of our case.

Conclusion: Two novel mutations in the ALMS1 gene causative for AS have been reported here, thereby increasing the number of reported mutations to 81 and providing a wider basis for mutational screening among affected individuals.

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Related in: MedlinePlus

DNA sequence analysis of Alstrom syndrome mutations. Proband is indicated by the solid circle and arrow. Smaller symbols represent individuals from whom DNA was unavailable. There is no known consanguinity between the parents of this kindred. Electrophoretic tracings for exons 6 and 17 of the ALMS1 gene from the proband and available immediate relatives are shown. The proband is a compound heterozygote for the V424I and H3882 Y mutations while the mother demonstrates heterozygosity only for the H3882Y mutation and the younger sister demonstrates heterozygosity only for the V424I mutation. The older sister has no mutations in the ALMS1 gene.
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Figure 1: DNA sequence analysis of Alstrom syndrome mutations. Proband is indicated by the solid circle and arrow. Smaller symbols represent individuals from whom DNA was unavailable. There is no known consanguinity between the parents of this kindred. Electrophoretic tracings for exons 6 and 17 of the ALMS1 gene from the proband and available immediate relatives are shown. The proband is a compound heterozygote for the V424I and H3882 Y mutations while the mother demonstrates heterozygosity only for the H3882Y mutation and the younger sister demonstrates heterozygosity only for the V424I mutation. The older sister has no mutations in the ALMS1 gene.

Mentions: Her family consisted of non-consanguineous parents, both alive and well, as well as four siblings – three sisters (aged 18, 26, 29 years) and one brother (aged 29 years), who were also healthy. The family structure is outlined in Figure 1.


Alstrom syndrome (OMIM 203800): a case report and literature review.

Joy T, Cao H, Black G, Malik R, Charlton-Menys V, Hegele RA, Durrington PN - Orphanet J Rare Dis (2007)

DNA sequence analysis of Alstrom syndrome mutations. Proband is indicated by the solid circle and arrow. Smaller symbols represent individuals from whom DNA was unavailable. There is no known consanguinity between the parents of this kindred. Electrophoretic tracings for exons 6 and 17 of the ALMS1 gene from the proband and available immediate relatives are shown. The proband is a compound heterozygote for the V424I and H3882 Y mutations while the mother demonstrates heterozygosity only for the H3882Y mutation and the younger sister demonstrates heterozygosity only for the V424I mutation. The older sister has no mutations in the ALMS1 gene.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2266715&req=5

Figure 1: DNA sequence analysis of Alstrom syndrome mutations. Proband is indicated by the solid circle and arrow. Smaller symbols represent individuals from whom DNA was unavailable. There is no known consanguinity between the parents of this kindred. Electrophoretic tracings for exons 6 and 17 of the ALMS1 gene from the proband and available immediate relatives are shown. The proband is a compound heterozygote for the V424I and H3882 Y mutations while the mother demonstrates heterozygosity only for the H3882Y mutation and the younger sister demonstrates heterozygosity only for the V424I mutation. The older sister has no mutations in the ALMS1 gene.
Mentions: Her family consisted of non-consanguineous parents, both alive and well, as well as four siblings – three sisters (aged 18, 26, 29 years) and one brother (aged 29 years), who were also healthy. The family structure is outlined in Figure 1.

Bottom Line: Mutations in the ALMS1 gene have been found to be causative for AS with a total of 79 disease-causing mutations having been described.Examination of her family revealed that her phenotypically unaffected mother and younger sister also had heterozygous mutations in the ALMS1 gene.Two novel mutations in the ALMS1 gene causative for AS have been reported here, thereby increasing the number of reported mutations to 81 and providing a wider basis for mutational screening among affected individuals.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Vascular Biology and Medicine, Robarts Research Institute and Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada. tjoy@uwo.ca

ABSTRACT

Background: Alstrom syndrome (AS) is a rare autosomal recessive disease characterized by multiorgan dysfunction. The key features are childhood obesity, blindness due to congenital retinal dystrophy, and sensorineural hearing loss. Associated endocrinologic features include hyperinsulinemia, early-onset type 2 diabetes, and hypertriglyceridemia. Thus, AS shares several features with the common metabolic syndrome, namely obesity, hyperinsulinemia, and hypertriglyceridemia. Mutations in the ALMS1 gene have been found to be causative for AS with a total of 79 disease-causing mutations having been described.

Case presentation: We describe the case of a 27-year old female from an English (Caucasian) kindred. She had been initially referred for hypertriglyceridemia, but demonstrated other features suggestive of AS, including blindness, obesity, type 2 diabetes, renal dysfunction, and hypertension. DNA analysis revealed that she is a compound heterozygote with two novel mutations in the ALMS1 gene - H3882Y and V424I. Examination of her family revealed that her phenotypically unaffected mother and younger sister also had heterozygous mutations in the ALMS1 gene. In addition to presenting these novel molecular findings for AS, we review the clinical and genetic features of AS in the context of our case.

Conclusion: Two novel mutations in the ALMS1 gene causative for AS have been reported here, thereby increasing the number of reported mutations to 81 and providing a wider basis for mutational screening among affected individuals.

Show MeSH
Related in: MedlinePlus