Table 1 Eight new pathogenic founder variants identified in two Israeli populations

Ashkenazi Jews

WFS1 NM_006005.3:c.1672C > T; p.Arg558Cys

Wolfram syndrome 1 (#606201)

Five individuals homozygous for this variant were observed in the Franklin community. Three of the patients’ ages ranged between 42 and 49. Phenotypes included Maturity Onset Diabetes of the Young (MODY, in all patients), optic atrophy (in three patients), urinary and fecal incontinence, cerebellar atrophy on MRI, and hearing impairment. This variant was previously reported as a causal variant for Wolfram syndrome with milder phenotypes with only 1/8 presenting with optic atrophy [30]. Our results show that optic atrophy might be more frequent than previously thought (3/5)

References: [21, 31]

1/68

2

PCDH15 NM_001384140.1:c.733C > T; p.Arg245*

Usher syndrome, type 1F (#602083)

Appeared in two affected cases in the Franklin community

References: [32, 33]

1/113

3

DDX11 NM_030653.4:c.1763-1G > C; p.?

Warsaw breakage syndrome (#613398)

Appeared in two affected cases in the Franklin community. It was recently added to the recommended Israeli variants panel (independent of our findings)

References: [26, 34]

1/113

3

EYS NM_001142800.2:c.9286_9295delGTAAATATCG; p.Val3096Leufs*28

Retinitis pigmentosa 25 (#602772)

Appeared in two affected cases in the Franklin community

Reference: [35]

1/113

3

VPS41 NM_014396.4:c.1984C > T; p.Arg662*

Spinocerebellar ataxia, autosomal recessive 29 (#619389)

A nonsense variant where LOF is the disease mechanism, for which no community evidence was found

Reference: [36]

1/113

3

TKT NM_001064.4:c.769_770insCTACCTCCTTATCTTCTG; p. Trp257delinsSerThrSerLeuSerSerGly

Short stature, developmental delay, and congenital heart defects (#617044). Also known as: Transketolase deficiency

No community evidence was found

Reference: [37]

1/145

3

CLCN1 NM_000083.3:c.1238 T > G; p.Phe413Cys

Congenital myotonia, autosomal recessive (#255700)

No community evidence was found

References: [38, 39]

1/145

3

Muslim Arabs

ACSF3 NM_001243279.3:c.1470G > C; p.Glu490Asp

Combined malonic and methylmalonic aciduria (#614265)

Appeared in two Muslim Arab cases in the Franklin community as a causal variant

Reference: [40]

1/154

3