Reduced penetrance in a large Caucasian pedigree with Stickler syndrome.
2017
ABSTRACTBackground: In a four-generation Caucasian family variably diagnosed with autosomal dominant (AD) Stickler or Wagner disease, commercial gene screening failed to identify a mutation in COL2A1 or VCAN. We utilized linkage mapping and
exome sequencingto identify the causal variant.Materials and methods: Genomic DNA samples collected from 40 family members were analyzed. A whole-genome linkage scan was performed using Illumina HumanLinkage-24 BeadChip followed by two-point and multipoint linkage analyses using FASTLINK and
MERLIN.
Exome sequencingwas performed on two affected individuals, followed by co-segregation analysis.Results: Parametric multipoint linkage analysis using an
ADinheritance
modeldemonstrated HLOD scores > 2.00 at chromosomes 1p36.13-1p36.11 and 12q12-12q14.1. SIMWALK multipoint analysis replicated the peak in chromosome 12q (peak LOD = 1.975). FASTLINK two-point analysis highlighted several clustered chromosome 12q SNPs with HLOD > 1.0.
Exome sequencingrevealed a novel nonsen...
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