Spectrum of ALMS1 variants and evaluation of genotype-phenotype correlations in Alström syndrome.

Spectrum of ALMS1 variants and evaluation of genotype-phenotype correlations in Alström syndrome. Research Abstract Details 

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Spectrum of ALMS1 variants and evaluation of genotype-phenotype correlations in Alström syndrome. Abstract Text:

Jan D Marshall,Elizabeth G Hinman,Gayle B Collin,Sebastian Beck,Rita Cerqueira,Pietro Maffei,Gabriella Milan,Weidong Zhang,David I Wilson,Tom Hearn, Tavares,Roberto Vettor,Caterina Veronese,Mitchell Martin,W Venus So,Patsy M Nishina, Naggert,

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.

Spectrum of ALMS1 variants and evaluation of genotype-phenotype correlations in Alström syndrome. Publishing Authors By Initials

JD Marshall,EG Hinman,GB Collin,S Beck,R Cerqueira,P Maffei,G Milan,W Zhang,DI Wilson,T Hearn,P Tavares,R Vettor,C Veronese,M Martin,WV So,PM Nishina,JK Naggert,

For similar pathological conditions, signs and symptoms: pathologic processes: disease: syndrome research abstracts see: pathological conditions, signs and symptoms: pathologic processes: disease: syndrome research

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Spectrum of ALMS1 variants and evaluation of genotype-phenotype correlations in Alström syndrome. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Human mutation

VOLUME: 28

Page Numbers: 1114-23

Journal Abbreviation: Hum. Mutat.

ISSN: 1098-1004

DAY: 3

MONTH: Nov

YEAR: 2007

Spectrum of ALMS1 variants and evaluation of genotype-phenotype correlations in Alström syndrome. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 9215429

Spectrum of ALMS1 variants and evaluation of genotype-phenotype correlations in Alström syndrome. Keywords Mesh Terms:

KEYWORDS: Syndrome

MESH TERMS: genetics

Chemical & Substance for Abstract: Spectrum of ALMS1 variants and evaluation of genotype-phenotype correlations in Alström syndrome. Information

Substance Name: DNA Primers

Registry Number: 0

Grant and Affiliation Information for Spectrum of ALMS1 variants and evaluation of genotype-phenotype correlations in Alström syndrome.

AFFILIATION: The Jackson Laboratory, Bar Harbor, Maine 04609, USA.

Country: United States

AGENCY: United States NICHD

GRANT: HD36878

ACRONYM: HD

MEDLINETA: Hum Mutat

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