Sudden unexpected fatal encephalopathy in adults with OTC gene mutations-Clues for early diagnosis and timely treatment

Table 3 OTC gene mutations identified in adult OTCD patients with fatal encephalopathy

Patient (sex; origin)	Mutation	Exon	Functional domain	Comment	Mutation reference	Genetic family testing
Pt 1 (M; Italy)	c.119G > T (p.Arg40Leu)	2	Polar/CP binding domain (S1)	CpG dinucleotide	This report	Three HT females: mother (76 y), two nieces (13 and 22 y); HM brother (50 y); WT sister
Pt 2 (M; Italy and Japan)	c.119G > A (p.Arg40His)	2	Polar/CP binding domain (S1)	CpG dinucleotide; protein degradation under certain conditions; reported OTC activity 6%	[[17]]	Not performed
Pt 3 (M; Italy)	c.314G > A (p.Gly105Glu)	4	Polar/CP binding domain (turn)	-	This report	HT mother (43 y); HM grandfather (80 y); WT brother
Pt 4 (M; Italy)	c.622G > A (p.Ala208Thr)	6	Equatorial/ORN binding domain (H6)	CpG dinucleotide; reported OTC activity 4%	[[19]]	HT daughter (36 y)
Pt 5 (F; Italy)	c.829C > T (p.Arg277Trp)	8	Equatorial/ORN binding domain (H9), flexible loop	CpG dinucleotide; increased k_m for ORN; reported OTC activity 5%	[[20]]	Three HT females: mother (72 y), sister (42 y) and niece (18 y); six WT females and two WT males

Abbreviations: M male, F female, CP carbamyl phosphate, ORN ornithine, S strand or $β$ -sheet, H $α$ -helix, HT heterozygous, HM hemizygous, WT wild type, y years of family members at the time of the proband’s acute episode.

ISSN: 1750-1172