FamilyLabel: Jiao_2004_Three_Families
Family#PresentingHPOs: N/A
FamilyPresentingHPOFreeText: The affected family members have been diagnosed with familial exudative vitreoretinopathy segregating with an autosomal recessive mode of inheritance.
FamilyNotHPOs: N/A
FamilyNotHPOFreeText: Although bone density measurements are not available, at least two of the affected individuals lack bone fractures in the first three decades of life, distinguishing their phenotype from osteoporosis-pseudoglioma syndrome.
CountryOrigin: The three families are reportedly of European descent.
Ethnicity: Not specifically described
Race: The three families are reportedly of European descent.
Family#PreviousTesting: Candidate-locus-directed linkage analysis focused on chromosome 11q, with maximum LOD score of 3.6 associated with the D11S987 microsatellite marker linked to a 311-Mb region.
Family#Method1: Genome-wide linkage analysis
Family#Method2: Sanger sequencing of the candidate gene LRP5
Family#GenotypingMethod: Candidate-locus-directed linkage analysis was initially performed on all three families, focused on chromosome 11q, with maximum LOD score of 3.6 associated with the D11S987 microsatellite marker linked to a 311-Mb region. Sanger sequencing of the candidate gene LRP5 locus was subsequently performed.
Affected: 6 genotyped
Unaffected: 0 genotyped (although 6 unaffected individuals are genotyped but ineligible because they are from previous generations that lack affected members.
Segregations: 3 segregations are shown by the three pedigrees in Figure 1.
PublishedLOD: 3.6
eLOD: N/A
AddSegregationInfo: While none of the families would individually be eligible for inclusion in segregation evidence using an estimated LOD score, the published LOD score is sufficient for their inclusion.
ProbandLabel: Jiao_2004_Family_68001_Proband, Jiao_2004_Family_68002_Proband, Jiao_2004_Family_68003_Proband
Variant: The affected family members harbor one of the following three variants in homozygous state; NM_002335.4(LRP5):c.2254C>G (p.Arg752Gly), NM_002335.4(LRP5):c.4099G>A (p.Glu1367Lys), or NM_002335.4(LRP5):c.1709G>A (p.Arg570Gln)
ClinVar: 6290, 6291, 6289
gnomAD: NM_002335.4(LRP5):c.2254C>G (p.Arg752Gly) was not found in gnomAD v2.1.1.
NM_002335.4(LRP5):c.4099G>A (p.Glu1367Lys) is present in gnomAD v2.1.1. at a frequency of 0.00001760 (2/113626) in the European non-Finnish population
https://gnomad.broadinstitute.org/variant/11-68204455-G-A?dataset=gnomad_r2_1
NM_002335.4(LRP5):c.1709G>A (p.Arg570Gln) was not found in gnomAD v2.1.1.
VariantEvidence: NM_002335.4(LRP5):c.2254C>G (p.Arg752Gly) is a missense variant in exon 10 of 23 that does not have experimental evidence of impact on the protein product. NM_002335.4(LRP5):c.4099G>A (p.Glu1367Lys) is a missense variant in exon 19 of 23 that does not have experimental evidence of impact on the protein product. NM_002335.4(LRP5):c.1709G>A (p.Arg570Gln) is a missense variant in exon 8 of 23 that does not have experimental evidence of impact on the protein product.
FamilyAddInfo: All three families are reportedly consanguineous.
FamilyPMIDs: N/A