Proteins linked to autosomal dominant and autosomal recessive disorders harbor characteristic rare missense mutation distribution patterns

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Proteins linked to autosomal dominant and autosomal recessive disorders harbor characteristic rare missense mutation distribution patterns.

The role of rare missense variants in disease causation remains difficult to interpret. We explore whether the clustering pattern of rare missense variants (MAF < 0.01) in a protein is associated with mode of inheritance. Mutations in genes associated with autosomal dominant (AD) conditions are known to result in either loss or gain of function, whereas mutations in genes associated with autoso...

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A Novel Missense Mutation in CLCN1 Gene in a Family with Autosomal Recessive Congenital Myotonia

Congenital recessive myotonia is a rare genetic disorder caused by mutations in CLCN1, which codes for the main skeletal muscle chloride channel ClC-1. More than 120 mutations have been found in this gene. The main feature of this disorder is muscle membrane hyperexcitability. Here, we report a 59-year male patient suffering from congenital myotonia. He had transient generalized myotonia, which...

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A Novel Autosomal Recessive GJA1 Missense Mutation Linked to Craniometaphyseal Dysplasia

Craniometaphyseal dysplasia (CMD) is a rare sclerosing skeletal disorder with progressive hyperostosis of craniofacial bones. CMD can be inherited in an autosomal dominant (AD) trait or occur after de novo mutations in the pyrophosphate transporter ANKH. Although the autosomal recessive (AR) form of CMD had been mapped to 6q21-22 the mutation has been elusive. In this study, we performed whole-...

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A missense mutation in LIM2 causes autosomal recessive congenital cataract

PURPOSE To identify mutations in the LIM2 gene in families with hereditary congenital or juvenile-onset cataract. METHODS Forty families (total of 100 affected and 84 unaffected individuals) were recruited for the study. Probands were screened for pathogenic alterations in 10 different candidate genes including the lens intrinsic membrane protein-2 (LIM2) gene. Exons and flanking regions were...

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A recurrent missense mutation in GJA3 associated with autosomal dominant cataract linked to chromosome 13q

PURPOSE To map and identify the genetic defect underlying autosomal dominant cataract segregating in a 5-generation Caucasian American family. METHODS Genomic DNA was prepared from blood leukocytes, genotyping was performed using microsatellite markers, and logarithm of the odds (LOD) scores were calculated using the LINKAGE programs. Mutation profiling was performed using direct exon cycle-s...

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ژورنال

عنوان ژورنال: Human Molecular Genetics

سال: 2015

ISSN: 0964-6906,1460-2083

DOI: 10.1093/hmg/ddv309