Case#:BV (per Bianchi et al)

CaseHPOs:

CaseHPOsFreeText: Febrile seizure at 18 months.

Variant: NM_001482.2:c.446G>A (p.Trp149Ter)

ClinVar: 7302

gnomAD: No listed (note Trp missense at 149)

VariantEvidence:

FamilyLabel: Bianchi family

FamilyPresentingHPOs:HP:0100543, HP:0025051, HP:0000750

(cognitive impairment, reduced brain creatine level by MRS, speech delay)

FamilyHPOsFreeText: Routine blood and urine analysis and extensive investigation for neurometabolic disorders was normal. increase in brain creatine when given oral creatine supplementation, low urine guanidinoacetate

FamilyNotHPOs: Normal brain MRI

CountryOrigin: Italy

ProbandLabel: Patient 1

FamilyPreviousTesting: 1H MRS revealed the total absenceof the Cr/PCr peak in the paraventricular white matter, inthe cerebellum, and in the parieto-occipital cortex. Blood concentrations of creatine and guanidinoacetate were normal, but urine guanidinoacetate and creatinine were low. Normal GAMT enzyme activity. Deficient AGAT activity (<0.3 nmol/hr/mg protein; normal 12.6-23.4), no GATM cDNA detected by RT-PCR.

FamilyMethod1: DGGE

FamilyMethod2: Sequencing

FamilyGenotypingMethod: Direct sequencing of exon 1; exons 2–9 and exon/intron boundaries screened by denaturing gradient gel electrophoresis (DGGE), followed by sequencing of exon 3 (with abnormal DGGE pattern).

Variant: NM_001482.2:c.446G>A (p.Trp149Ter)

ClinVar: 7302

FamilyAddInfo: Sequence analysis showed that parents are heterozygous.

FamilyPMIDs: 10762163 (Bianchi et al)