Patient 1
Case: Patient 1, female, AOR 2 years, Turkish
CasePresentingHPOs: HP:0001561, HP:0003265, HP:0001270, HP:0000924, HP:0000253, HP:0002007, HP:0000520, HP:0005280, HP:0003196, HP:0000463, HP:0005306, HP:0000212, HP:0000347, HP:0005619, HP:0002938, HP:0000960, HP:0009826, HP:0001156, HP:0004060, HP:0100543, HP:0008936, HP:0007340, HP:0001265, HP:0005193, HP:0002063, HP:0002240, HP:0001407, HP:0100625, HP:0004565, HP:0005619, HP:0002867, HP:0100865, HP:0003016, HP:0003416, HP:0002176, HP:0006532, HP:0000670, HP:0004315, HP:0002850,
CaseNOTHPOs: HP:0000365, HP:0000504
CasePreviousTesting: Lab examines including urine organic acid analysis (urine glycosaminoglycan/ GAG and lysosomal enzymes), tandem mass screening, chromosome analysis, electroencephalogram were unremarkable. Negative for mutations in SLC35D1 (Schneckenbecken dysplasia MIM 269250), and INPPL1 (opsismodysplasia; MIM 258480) .
CaseGenotypingMethod: WES
Variant: NM_001440.3: c.953C>T(p.P318L)
CA ID: CA370858101
Homozygous
gnomAD: no homozygotes, only 2 hets in Euro-ND populatin CA370858101
AddCaseInfo: Parents were also tested by WES and were both found to be carriers of the mutation.
VariantEvidence: WEstern blot analysis of EXTL3 from patinet 1 cells shows expression of hte P318L variant (Figure 1B), indicating the protein is still produced. However, a glycosyltransferase assay using the wildtype EXTL3 and th eP318L variant showed reduced enzyme activity in the P318L variant compared to wildtype, and simiar levels of activity as untransfected/ mock controls. This indicates the P318L mutation acts as a loss of protein function of the enzyme activity.