Subject 4
Case# Subject 4, M, 8yo onset, Hispanic
CasePresentingHPOs HP:0001249, HP:0001289, HP:0002066, HP:0009053, HP:0007340, HP:0001987, HP:0002925, HP:0005184, HP:0002058, HP:0002169, HP:0003201, HP:0001250, HP:0003236, HP:0000821, HP:0006801
HPOcont: Intellectual Disability, Confusion, Gait ataxia, Lower limb muscle weakness, Dysarthria, Hyperammonemia, Elevated TSH, Prolonged QTc interval, Myopathic facies, Clonus, Rhabdomyolysis, Seizures, Elevated CPK, Hypothyroidism, Brisk DTR
HPOFreeText: (2 years) uncoordinated gait and intellectual disability. (8 years) disorientation, ataxic gait, weakness in lower extremities, and dysarthria. (12 years) myopathic facies, brisk tendom reflexes, clonus, and impaired gait.
CaseNotHPOs HP:0001943, HP:0002151, HP:0002913
NotHPOcont: Hypoglycemia, Elevated Lactate, Myoglobinuria
CasePreviousTesting "lactate and glucose normal; elevated ammonia(111 μmol/l), elevated CPK (16,674 U/l). Urine was negative for myoglobin. TSH level was increased to 30.8 μIU/ml (range 0.32–5.00 μIU/ml), T3 was 166 ng/dl (range 90–260 ng/dl), and T4 was 5.2 μg/dl (range 6.4–13.3 μg/dl). Urine organic acids were normal."Muscle biopsy showed normal respiratory chain studies. Mitochondrial genome sequencing for common point mutations and deletions were normal."
CaseMethod1 WES
CaseMethod2 Sanger
CaseGenotypingMethod WES and cSNP results confirmed with Sanger
Variant (1) NM_152906.6:c.460G>A (p.Gly154Arg)
ClinVar (1) 208823
CAID (1) CA358646
gnomAD (1) 0.001549(Other), 0.0001208(Overall)
VariantEvidence (Figure 3) using "EBV-transformed B-lymphoblastoid cell lines (BLCLs) from subject 4 with homozygous c.460G>A (p.Gly154Arg) mutation, and evaluated the Golgi by intracellular staining with WGA, as well as cis Golgi marker, anti-GM130 antibody." WGA stain resolved lower area of golgi bodies in p.Gly154Arg cells than WT. Measured immunoglobulin heavy chain binding protein levels in WT and and patient fibroblasts, BiP levels in patient cells lower than WT after ER induced stress by Brefeldin A.
CaseAddInfo nonsanguineous, confirmed heterozygosity of both parents
CasePMIDs n/a