Alström syndrome: intrafamilial phenotypic variability in sibs with a novel nonsense mutation of the <i>ALMS1</i> gene

Titomanlio, Luigi; Brasi, Daniele De; Buoninconti, Anna; Sperandeo, Maria Pia; Pepe, Antonio; Andria, Generoso; Sebastio, Gianfranco

doi:10.1111/j.0009-9163.2004.00204.x

Cited by 22 publications

(19 citation statements)

References 5 publications

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“…24 Direct sequencing of ALMS1 has identified 79 different mutations, clustering in exons 8, 10, and 16, in patients with Alström syndrome. 33,34 Although ALMS1 polymorphisms are common in the general population, no evidence was found of an association between common variants of the gene and type 2 diabetes mellitus.…”

Section: Discussionmentioning

confidence: 99%

“…37 The ALMS1 protein is widely expressed in human tissues, but its function is unknown. 33 The pathophysiology of Alström syndrome is thought to be related to defects in microtubule organization and intracellular transport. 38 The development of CAD has not been found to be affected in individuals with Alström syndrome although a case of premature-onset CAD was recently described in the longest surviving patient with this syndrome.…”

Section: Discussionmentioning

confidence: 99%

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Identification of a Glutamic Acid Repeat Polymorphism of ALMS1 as a Novel Genetic Risk Marker for Early-Onset Myocardial Infarction by Genome-Wide Linkage Analysis

Ichihara

Yamamoto

Asano

et al. 2013

Circ Cardiovasc Genet

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Two major approaches to the identification of susceptibility genes for CAD or MI have been adopted: genome-wide population-based case-control studies and genome-wide linkage studies (GWLSs), with the latter representing a comprehensive Background-Myocardial infarction (MI) is a leading cause of death worldwide. Given that a family history is an independent risk factor for coronary artery disease, genetic variants are thought to contribute directly to the development of this condition. The identification of susceptibility genes for coronary artery disease or MI may thus help to identify high-risk individuals and offer the opportunity for disease prevention. Methods and Results-We designed a 5-step protocol, consisting of a genome-wide linkage study followed by association analysis, to identify novel genetic variants that confer susceptibility to coronary artery disease or MI. A genome-wide affected sib-pair linkage study with 221 Japanese families with coronary artery disease yielded a statistically significant logarithm of the odds score of 3.44 for chromosome 2p13 and MI. Further association analysis implicated Alström syndrome 1 gene (ALMS1) as a candidate gene within the linkage region. Validation association analysis revealed that representative single-nucleotide polymorphisms of the ALMS1 promoter region were significantly associated with earlyonset MI in both Japanese and Korean populations. Moreover, direct sequencing of the ALMS1 coding region identified a glutamic acid repeat polymorphism in exon 1, which was subsequently found to be associated with early-onset MI. Conclusions-The

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Identification of a Glutamic Acid Repeat Polymorphism of ALMS1 as a Novel Genetic Risk Marker for Early-Onset Myocardial Infarction by Genome-Wide Linkage Analysis

Ichihara

Yamamoto

Asano

et al. 2013

Circ Cardiovasc Genet

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“…To date, 24 mutations in ALMS1 have been reported in patients with Alström syndrome. The majority of these are nonsense and frameshift variations (insertions or deletions) that are predicted to cause premature protein truncation [Collin et al, 2002;Hearn et al, 2002;Kinoshita et al, 2003;Titomanlio et al, 2004;Bond et al, 2005;Minton et al, 2006].…”

Section: Introductionmentioning

confidence: 99%

Spectrum ofALMS1variants and evaluation of genotype-phenotype correlations in Alström syndrome

et al. 2007

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Alström syndrome is a monogenic recessive disorder featuring an array of clinical manifestations, with systemic fibrosis and multiple organ involvement, including retinal degeneration, hearing loss, childhood obesity, diabetes mellitus, dilated cardiomyopathy (DCM), urological dysfunction, and pulmonary, hepatic, and renal failure. We evaluated a large cohort of patients with Alström syndrome for mutations in the ALMS1 gene. In total, 79 disease-causing variants were identified, of which 55 are novel mutations. The variants are primarily clustered in exons 8, 10, and 16, although we also identified novel mutations in exons 12 and 18. Most alleles were identified only once (45/79), but several were found recurrently. Founder effects are likely in families of English and Turkish descent. We also identified 66 SNPs and assessed the functional significance of these variants based on the conserved identity of the protein and the severity of the resulting amino acid substitution. A genotype-phenotype association study examining 18 phenotypic parameters in a subset of 58 patients found suggestive associations between disease-causing variants in exon 16 and the onset of retinal degeneration before the age of 1 year (P = 0.02), the occurrence of urological dysfunction (P = 0.02), of DCM (P = 0.03), and of diabetes (P = 0.03). A significant association was found between alterations in exon 8 and absent, mild, or delayed renal disease (P = 0.0007). This data may have implications for the understanding of the molecular mechanisms of ALMS1 and provides the basis for further investigation of how alternative splicing of ALMS1 contributes to the severity of the disease.

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“…With an estimated prevalence of < 1:100 000, only ~500 cases of AS have been reported in the literature thus far. (3,11,13,(17)(18)(19)(20) Since the condition was first described in 1959, (7)(8). The diagnosis of Alström syndrome is based on cardinal clinical features that emerge throughout infancy, childhood, and young adulthood.…”

Section: Discussionmentioning

confidence: 99%

ALSTROM Syndrome (Cases presentation and review of literature)

Al-Kaabi¹

2017

IJPN

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Alström syndrome: intrafamilial phenotypic variability in sibs with a novel nonsense mutation of the ALMS1 gene

Cited by 22 publications

References 5 publications

Identification of a Glutamic Acid Repeat Polymorphism of ALMS1 as a Novel Genetic Risk Marker for Early-Onset Myocardial Infarction by Genome-Wide Linkage Analysis

Identification of a Glutamic Acid Repeat Polymorphism of ALMS1 as a Novel Genetic Risk Marker for Early-Onset Myocardial Infarction by Genome-Wide Linkage Analysis

Spectrum ofALMS1variants and evaluation of genotype-phenotype correlations in Alström syndrome

ALSTROM Syndrome (Cases presentation and review of literature)

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