PhenoModifier-Variant Detail

Variant "PDZD7:c.682G>A(p.Gly228Arg)"

Search result: 1 record

Variant information

Gene:

PDZD7

Variant:

PDZD7:c.682G>A(p.Gly228Arg)

Genomic location:

chr10:102782003(hg19)

HGVS:

SO Term	RefSeq
protein_coding	NM_001195263.1:c.682G>A(p.Gly228Arg)
protein_coding	NM_024895.4:c.682G>A(p.Gly228Arg)

dbSNP ID:

rs753034799

GWAS trait:

no data

Modifier statisitcs

Record:

1

Disorder:

1

Reference:

1

Effect type:

Expressivity(1)

Modifier effect:

Risk factor(1)

Detail：

Target disease:

Diabetes Mellitus (DOID_9351)

Effect type:

Expressivity

Modifier effect:

Risk factor

Evidence:

Pedigree analysis

Effect:

Mutations in PDZD7 have been described to modify the retinal phenotype of USH2 or have been implicated in digenic USH.

Reference:

PMID26416264

Title:

PDZD7 and hearing loss: More than just a modifier.

Species studied:

Human

Abstract:

Deafness is the most frequent sensory disorder. With over 90 genes and 110 loci causally implicated in non-syndromic hearing loss, it is phenotypically and genetically heterogeneous. Here, we investigate the genetic etiology of deafness in four families of Iranian origin segregating autosomal recessive non-syndromic hearing loss (ARNSHL). We used a combination of linkage analysis, homozygosity mapping, and a targeted genomic enrichment platform to simultaneously screen 90 known deafness-causing genes for pathogenic variants. Variant segregation was confirmed by Sanger sequencing. Linkage analysis and homozygosity mapping showed segregation with the DFNB57 locus on chromosome 10 in two families. Targeted genomic enrichment with massively parallel sequencing identified causal variants in PDZD7: a homozygous missense variant (p.Gly103Arg) in one family and compound heterozygosity for missense (p.Met285Arg) and nonsense (p.Tyr500Ter) variants in the second family. Screening of two additional families identified two more variants: (p.Gly228Arg) and (p.Gln526Ter). Variant segregation with the hearing loss phenotype was confirmed in all families by Sanger sequencing. The missense variants are predicted to be deleterious, and the two nonsense mutations produce null alleles. This report is the first to show that mutations in PDZD7 cause ARNSHL, a finding that offers addition insight into the USH2 interactome. We also describe a novel likely disease-causing mutation in CIB2 and illustrate the complexity associated with gene identification in diseases that exhibit large genetic and phenotypic heterogeneity.