Figure 2Haplotype Analysis Performed in Six Families with H SyndromeAffected individuals are marked by gray symbols. The disease-associated haplotypes in the linked interval on chromosome 10q21.3–q22.1 are shown by vertical bars (red and green) in families A–F. Alleles excluded by recombination events are marked in pink. The physical locations of the polymorphic microsatellites are given near the haplotype for individual AI-2.
Case: Family A Proband AII-8, male, Arabic, Israeli, 13yo at report
CasePresentingHPOs: HP:0000953, HP:0000998, HP:0000054, HP:0001433, HP:0011025, HP:0000365, HP:0000520, HP:0012385, HP:0001684, HP:0000823, HP:0030053, HP:0100324, HP:0100727
CasePresentingHPOsFreeText: Scrotal masses, Dilated scleral vessels
CaseNOTHPOs: HP:0008064, HP:0002619, HP:0007380
CaseNOTHPOSFreeText:
CasePreviousTesting: direct sequencing of AIFM2, ADAMTS14, EIF4EBP2, C10ORF54, PPA1, H2AFY2, LRRC20, NODAL, PRF1, TYSND1, SAR1A, PSAP, NPFFR1, and C10ORF27
CaseGenotypingMethod: microarray, haplotype analysis, direct sequencing of exons of SLC29A3, restriction digestion
Variant: G427S; G437R
ClinVarID: or CAID: 563/CA114349; 565/CA114352
gnomAD: The missense variant G427S is present in gnomAD v4.0.0 with a MAF=0.00005339 (4/74926 alleles) in the African/African American population and 0 homozygotes. The missense variant G437R is present in gnomAD v4.0.0 with a MAF=0.00006666 (4/60002 alleles) in the Admixed American population and 0 homozygotes.
AddCaseInfo: consanguineous parents; mother was het for G427S, but father's genotype was not provided
PreviouslyPublished: PMID: 18410979
VariantEvidence: Functional studies in Xenopus oocytes demonstrated that G427S results in a total loss of transport activity (Kang et al. 2010; PMID: 20595384).
Kang et al. (2010) performed functional characterization of the G437R mutation in Xenopus oocytes and observed transport activity that was approximately half that of wildtype SLC29A3. Studies in NIH 3T3 fibroblasts demonstrated accelerated turnover of the G437R mutant compared to wildtype, suggesting decreased stability.