Table 1. CUL3 and KLHL3 variants segregating with the FHHt phenotype in each pedigree.

The zygosity of affected individuals within each pedigree for the causative variant is shown. Conservation describes the KLHL3 amino acid residues conserved across species expressed as the proportion of species sharing the same reference allele in primates (P), mammals (M) and vertebrates (V) (Ensemble KLHL3 paralogues; available at http://www.ensembl.org/Homo_sapiens/Gene/Compara_Ortholog?g=ENSG00000146021;r=5:136953189-137071779). The country of origin of each pedigree is also shown. Variants are described according to Human Genome Variation Society (HGVS) standard nomenclature using the reference sequences listed in Supplementary Table S2 (at http://www.clinsci.org/cs/126/cs1260721add.htm). *Previously undescribed variants; **previously undescribed genotype.

Pedigree	Gene	Genomic DNA position	HGVS coding DNA position	Zygosity	rs_identity	Protein effect	Conservation	Country of origin
1*	CUL3	Chr2:225368368	c.1377+1G>T	Heterozygous	–	Exon 9/intron 9 splicing	–	U.K.
2	CUL3	Chr2:225368368	c.1377+1G>C	Heterozygous	rs199469660	Exon 9/intron 9 splicing	–	Australia
3*	CUL3	Chr2:225368551	c.1207–12T>A	Heterozygous	–	Exon 9/intron 8 splicing	–	Australia
4	CUL3	Chr2:225368540	c.1207–1G>A	Heterozygous	rs199469654	Exon 9/intron 8 splicing	–	U.K.
5**	KLHL3	Chr5:136964078	c.1499G>T	Homozygous	–	G500V	P (9/9), M (37/37), V (49/50)	U.K.
6/7/8	KLHL3	Chr5:136974701	c.1160T>C	Heterozygous	rs199469630	L387P	P (9/9), M 33/33), V (46/46)	Australia
9	KLHL3	Chr5:136975551	c.1019C>T	Heterozygous	rs199469628	A340V	P (9/9), M 30/31), V (43/44)	Australia
10	KLHL3	Chr5:136964097	c.1480G>A	Heterozygous	rs199469633	A494T	P (9/9), M 36/36),	U.K.