Table 1. Digenic inheritance of the ALDH2 rs671 defective allele and ADH5 biallelic mutations identified in AMeDS individuals.

Family ID	Individual ID	Sex	Initial diagnosis*	ADH5 mutations		ALDH2 mutations		Hematological abnormalities**	Other complications***	Remarks****
				Allele1	Allele2	Allele1	Allele2
1	N0608	F	FA	p.W322*	p.W322*	p.E504K	WT	NA	NA	UPD (ADH5 locus)
2	N0611	F	AA	Splicing c.564+1G>A	p.A278P	p.E504K	WT	NA	NA
	Father2		Normal	c.564+1G>A	WT	p.E504K	WT
	Sibling2-1	F	Normal	WT	WT	WT	WT
3	N0614	M	AA	p.W322*	p.A278P	p.E504K	WT	NA	NA
4	N1037	F	BS	p.W322*	p.W322*	p.E504K	p.E504K	MDS (2)	SS (n.d.), MC, MD, NR, TC, HP, ID	Died from interstitial pneumonia (9 years)
	N1254	F	RA	p.W322*	p.W322*	p.E504K	p.E504K	AML (2)	SS (−5.2), MC, MD, NR, TC	Died after BMT (3 years)
	Father4		Normal	p.W322*	WT	p.E504K	p.E504K
	Mother4		Normal	p.W322*	WT	p.E504K	WT
	Sibling4-1	F	Normal	p.W322*	WT	p.E504K	p.E504K
5	N1267	F	DS	p.W322k	p.A278P	p.E504K	WT	MDS (7)	SS (−5.4), MC, MG, PLSVC, ID	Alive after second BMT (14 years)
	Sibling5-1	M	Normal	WT	WT	p.E504K	WT
6	N1269	F	FA	p.W322*	p.W322*	p.E504K	WT	MDS (3)	SS (−4.0), MD, ASD, ADHD, ID	Alive after BMT (8 years)
	N1270	M	FA	p.W322*	p.W322*	p.E504K	p.E504K	MDS (0)	SS (−4.7), MC (−5.8), MD, TC, AH, GA, HP, ID	Died from an infection (2 years)
	Father6		Normal	p.W322*	WT	p.E504K	WT
	Mother6		Normal	p.W322*	WT	p.E504K	WT
	Sibling6-1	F	Normal	WT	WT	p.E504K	WT
	Sibling6-2	F	Normal	p.W322*	WT	p.E504K	WT
7	N1275	F	FA	p.W322*	p.A278P	p.E504K	WT	MDS (8)	MC, SS (−4.1), HP, UH, DC, HD, LD, ID	Alive after BMT (12 years)
	Father7		Normal	p.W322*	WT	WT	WT
	Mother7		Normal	p.A278P	WT	p.E504K	WT
	Sibling7-1	F	Normal	WT	WT	WT	WT
8	N1329	M	FA	p.W322*	p.A278P	p.E504K	WT	MDS (12)	MC, SS (−3.2), HP, ID, PP	Alive (16 years)
	Father8		Normal	p.W322*	WT	p.E504K	p.E504K
	Sibling8-1		Normal	WT	WT	p.E504K	WT
9	NAG16714	F	Normal	p.S75N	p.S75N	WT	WT			No previous disease (55 years)

Affected individuals and Nagahama case are shown in bold.

*FA, Fanconi anemia; AA, aplastic anemia; RA, refractory anemia; BS, Bloom syndrome; DS, Dubowitz syndrome.

**Ages at onset are in parentheses. MDS, myelodysplastic syndromes; AML, acute myeloid leukemia. NA, not analyzed.

***SD in parentheses. n.d., not determined; SS, short stature; MC, microcephaly; MD, motor deterioration; NR, nasal ridge; TC, telecanthus; HP, hyperpigmentation; ID, intellectual disability; MG, micrognathia; PLSVC, persistent left superior vena cava; ASD, autistic spectrum disorder; ADHD, attention-deficit hyperactivity disorder; AH, adrenal hypoplasia; GA, gonadal abnormality; UH, uterus hypoplasia; DC, dolichocephaly; HD, hyperdactyly (long thumb); LD, learning disability; PP, Precocious puberty.

****UPD, uniparental isodisomy; BMT, bone marrow transplant.