Homozygosity Mapping of Alstrom Syndrome to Chromosome 2p

Abstract

Alström syndrome is a rare autosomal recessive disorder characterized by pigmentary retinal degeneration, sensorineural hearing loss, childhood obesity, non-insulin-dependent diabetes mellitus, hyperlipidemia and chronic nephropathy. Features occasionally observed include acanthosis nigricans, hypogonadism, hypothyroidism, alopecia, short stature and cardiomyopathy. We report here the results of a linkage study in a large French Acadian kindred, as a first step in identifying the molecular basis of Alström syndrome. Evidence of a founder effect made if feasible to use a homozygosity mapping strategy to identify the chromosomal location of the Alström gene. In a genome-wide screen, haplotype sharing for a region on chromosome 2 was observed in all affected individuals. Two point linkage analysis resulted in a maximum lod score of 3.84 (theta = 0.00) for marker D2S292. By testing additional markers, the disease gene was localized to a 14.9 cM region on chromosome 2p.

Refinement of genetic localization of the Alström syndrome on chromosome 2p12-13 by linkage analysis in a North African family

“…These data extend to another ethnic population findings made previously in a genetic isolate of French Acadians [5].…”

Refinement of genetic localization of the Alström syndrome on chromosome 2p12-13 by linkage analysis in a North African family

“…These data extend to another ethnic population findings made previously in a genetic isolate of French Acadians [5].…”

Mutations in ALMS1 cause obesity, type 2 diabetes and neurosensory degeneration in Alström syndrome

“…All five affected subjects from the extended pedigree were homozygous with respect to the insertion. Transmission of the insertion allele in unaffected carriers is consistent with previously reported haplotypes 6 . The insertion allele was not seen in 100 unrelated individuals from the general population.…”

The continuing failure to recognise Alström syndrome and further evidence of genetic homogeneity: Figure 1

“…Markers D2S136 and D2S286 delineate the criti-cal region of 10 cM in our families. D2S136 lies 4 cM telomeric to the minimal critical region reported by Macari et al ,5 while our centromeric boundary (D2S286) is coincident with that of Collin et al 4. Using MLINK,6 a maximum two point lod score of +4.62 was obtained for the marker D2S2113 at θ=0.…”

Refinement of genetic localization of the Alström syndrome on chromosome 2p12-13 by linkage analysis in a North African family

“…These data extend to another ethnic population findings made previously in a genetic isolate of French Acadians [5].…”

Mutations in ALMS1 cause obesity, type 2 diabetes and neurosensory degeneration in Alström syndrome

“…All five affected subjects from the extended pedigree were homozygous with respect to the insertion. Transmission of the insertion allele in unaffected carriers is consistent with previously reported haplotypes 6 . The insertion allele was not seen in 100 unrelated individuals from the general population.…”

The continuing failure to recognise Alström syndrome and further evidence of genetic homogeneity: Figure 1

“…Markers D2S136 and D2S286 delineate the criti-cal region of 10 cM in our families. D2S136 lies 4 cM telomeric to the minimal critical region reported by Macari et al ,5 while our centromeric boundary (D2S286) is coincident with that of Collin et al 4. Using MLINK,6 a maximum two point lod score of +4.62 was obtained for the marker D2S2113 at θ=0.…”

Refinement of genetic localization of the Alström syndrome on chromosome 2p12-13 by linkage analysis in a North African family

“…These data extend to another ethnic population findings made previously in a genetic isolate of French Acadians [5].…”

Mutations in ALMS1 cause obesity, type 2 diabetes and neurosensory degeneration in Alström syndrome

“…All five affected subjects from the extended pedigree were homozygous with respect to the insertion. Transmission of the insertion allele in unaffected carriers is consistent with previously reported haplotypes 6 . The insertion allele was not seen in 100 unrelated individuals from the general population.…”

The continuing failure to recognise Alström syndrome and further evidence of genetic homogeneity: Figure 1

“…Markers D2S136 and D2S286 delineate the criti-cal region of 10 cM in our families. D2S136 lies 4 cM telomeric to the minimal critical region reported by Macari et al ,5 while our centromeric boundary (D2S286) is coincident with that of Collin et al 4. Using MLINK,6 a maximum two point lod score of +4.62 was obtained for the marker D2S2113 at θ=0.…”