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 E Proband EII-1, male, Arabic, Israeli, 17yo at report
CasePresentingHPOs: HP:0000953, HP:0030053, HP:0000998, HP:0000054, HP:0000771, HP:0002619, HP:0001433, HP:0000520, HP:0012385, HP:0003565
CasePresentingHPOsFreeText: scrotal masses, dilated scleral vessels, maturation arrest in all tubules with few spermatids in 4% to 5% of the tubules on testicular biopsy
CaseNOTHPOs: HP:0008064, HP:0011025, HP:0000365, 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: G437R homozygous
ClinVarID: or CAID: 565/CA114352
gnomAD: 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, heterozygous, unaffected parents.
PreviouslyPublished: PMID: 18410979
VariantEvidence: Kang et al. (2010; PMID: 20595384) 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.