Genetic heterogeneity in Gaucher disease.

Zlotogora, Joël; Zaizov, Rina; Klibansky, Chaya; Matoth, Y; Bach, Gideon; Cohen, T.

doi:10.1136/jmg.23.4.319

Cited by 11 publications

(2 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…First, the SNPs defining the 'at-risk-haplotype' may not have been identified and genotyped yet; the SNP density in the replication sample does not allow any firm conclusion on this matter. Second, genetic and allelic heterogeneity within this ethnically homogeneous population cannot be excluded; such situations have been encountered for several monogenic traits 43,44 and might also apply to complex multifactorial traits. Third, an ancestral recombination event between the SNPs, rs9321501 and rs11154801, might have led the causative SNP to be found on complementary haplotypes in the two cohorts.…”

Section: Discussionmentioning

confidence: 99%

AHI1, a pivotal neurodevelopmental gene, and C6orf217 are associated with susceptibility to schizophrenia

Amann‐Zalcenstein

Avidan

Kanyas³

et al. 2006

Eur J Hum Genet

View full text Add to dashboard Cite

Schizophrenia, a severe neuropsychiatric disorder, is believed to involve multiple genetic factors. A significant body of evidence supports a pivotal role for abnormalities of brain development in the disorder. Linkage signals for schizophrenia map to human chromosome 6q. To obtain a finer localization, we genotyped 180 single nucleotide polymorphisms (SNPs) in a young, inbred Arab-Israeli family sample with a limited number of founders. The SNPs were mostly within a B7 Mb region around the strong linkage peak at 136.2 Mb that we had previously mapped. The most significant genetic association with schizophrenia for single SNPs and haplotypes was within a 500 kb genomic region of high linkage disequilibrium (LD) at 135.85 Mb. In a different, outbred, nuclear family sample that was not appropriate for linkage analysis, under-transmitted haplotypes incorporating the same SNPs (but not the individual SNPs) were significantly associated with schizophrenia. The implicated genomic region harbors the Abelson Helper Integration Site 1 (AHI1) gene, which showed the strongest association signal, and an adjacent, primate-specific gene, C6orf217. Mutations in human AHI1 underlie the autosomal recessive Joubert Syndrome with brain malformation and mental retardation. Previous comparative genomic analysis has suggested accelerated evolution of AHI1 in the human lineage. C6orf217 has multiple splice isoforms and is expressed in brain but does not seem to encode a functional protein. The two genes appear in opposite orientations and their regulatory upstream regions overlap, which might affect their expression. Both, AHI1 and C6orf217 appear to be highly relevant candidate genes for schizophrenia.

show abstract

Section: Discussionmentioning

confidence: 99%

AHI1, a pivotal neurodevelopmental gene, and C6orf217 are associated with susceptibility to schizophrenia

Amann‐Zalcenstein

Avidan

Kanyas³

et al. 2006

Eur J Hum Genet

View full text Add to dashboard Cite

show abstract

“…Virtually all inborn errors of metabolism, including lysosomal storage diseases, demonstrate some degree of variability in clinical expression. However, because of common genetic material, intrafamilial variation is, on average, less than interfamilial variation [MacFaul et al, 1982;Roubicek et al, 1985;Zlotogora et al, 1986;van de Kamp et al, 19813. Therefore, families are typically counseled that clinical progression of a lysosomal storage disease in a full sib is likely to follow a roughly similar clinical course to that of the proband.…”

mentioning

confidence: 99%

Intrafamilial variability in Hurler syndrome and Sanfilippo syndrome type A: Implications for evaluation of new therapies

et al. 1993

View full text Add to dashboard Cite

Intrafamilial variability has not been reported previously in Hurler syndrome or Sanfilippo syndrome type A. We describe two families in which sibs with comparable deficiencies of alpha-iduronidase (Hurler) or sulfamidase (Sanfilippo type A) activities in vitro nonetheless have divergence in clinical severity and disease progression. These cases underscore the need for caution in counseling as well as the limitations of using sibs as controls in evaluating the outcome of treatment.

show abstract

Intrafamilial variability in lysosomal storage diseases

Zlotogora

1987

Am. J. Med. Genet.

View full text Add to dashboard Cite

In most lysosomal storage diseases clinical variability is found and affects age-of-onset, severity, and the degree of neurological involvement. Very often the variability is due to the existence of different mutations leading to the same enzyme deficiency. In most of the families with more than one person affected, the clinical picture is very similar. Intrafamilial variation has been reported in the lysosomal storage diseases related or not related to genetic heterogeneity. In families in which different affected persons have the same genotype, as in X-linked disorders, or autosomal recessive diseases in which both parents of the affected sibs are carriers and healthy, the variability must be due to factors not related to the genotype. On the other hand, when different mutations are present in the same family, the variability may be related to the differences in the genotype of the affected persons. Knowledge of the possibility of intrafamilial variability and its genetic basis is essential in clinical and prenatal diagnosis of the lysosomal storage diseases.

show abstract

Genetic heterogeneity in Gaucher disease.

Cited by 11 publications

References 15 publications

AHI1, a pivotal neurodevelopmental gene, and C6orf217 are associated with susceptibility to schizophrenia

AHI1, a pivotal neurodevelopmental gene, and C6orf217 are associated with susceptibility to schizophrenia

Intrafamilial variability in Hurler syndrome and Sanfilippo syndrome type A: Implications for evaluation of new therapies

Intrafamilial variability in lysosomal storage diseases

Contact Info

Product

Resources

About