Table 3 Clinical features, affected genes and characteristics of new genetic variations identified for studied patients with ichthyosis

Phenotype

Sex

M

F

M

F

F

M

M

F

M

M

F

Age at diag*

3

1

6

35

4

34

74

1

19

14

15

Collodion baby

P

P

P

A

A

ND

P

P

P

P

A

Plate like scales

P

A

P

A

A

A

A

P

P

P

A

Fine scales

A

P

A

P

P

P

P

A

A

A

P

Scale color

Brown

White

Black

Brown

Brown

White

White

Brown

Black

Brown

White

Erythema

P

P

A

P

A

P

P

A

P

A

P

Ectropion

P

P

A

A

A

A

P

P

P

A

A

Alopecia

A

A

A

A

A

A

P

A

A

A

A

Palmo hyper

P

A

P

A

A

Severe

Severe

P

P

P

P

Pseudo Ainhum

A

A

A

A

A

P

A

A

P

A

A

Brachydactyly

A

A

A

A

A

A

P

P

P

A

P

Ear Deformity

A

A

A

A

A

A

A

P

P

A

A

Folds Involvement

P

A

P

A

Inguial

A

P

P

P

A

P

Diagnosis

CIE

CIE

LI

ILC

ILC

CIE

CIE

LI

LI

LI

CIE^•

Genotype

Affected Gene

NIPAL4

NIPAL4

NIPAL4

ABCA12

ABCA12

NIPAL4

TGM1

TGM1

TGM1

CYP4F22

CERS3

Mutation

c.118C > T^N

c.118C > T^N

c.118C > T^N

c.2855A > G^N

c.5898G > C^N

c.2855A > G^N

c.5898G > C^N

c.534A > C^R

c.788G > A^R

c.788G > A^R

c.1042C > T^R

c.844C > T^R

c.(999 + 1_1000-1)_(*1_?)del

State

H

H

H

H/H

H/H

H

H

H

H

H

H

State in literature [Ref]

–

–

–

–

–

H [46, 49]

H [42, 51]

C.het [52]

H [42, 51]

C.het [52]

C.het

[51, 53]

C.het [30]

H [29]

H [44]

Exon

1

1

1

18; 37

18;37

4

5

5

7

8

13

Bioinformatic prediction (score)

Polyphen2

0.808⁽⁺⁾

0.808 ⁽⁺⁾

0.808⁽⁺⁾

0.899⁽⁺⁺⁾

0.899⁽⁺⁺⁾

0.004^(Φ)

–

–

–

0.955⁽⁺⁾

–

SIFT

0.036^(#)

0.036^(#)

0.036^(#)

0; 0.008^(##)

0; 0.008^(##)

0.03^(#)

–

–

–

0^(##)

–

Mutation Taster

0.995^(ψ)

0.995^(ψ)

0.995^(ψ)

1^(ψ);0.999^(ψψ)

1^(ψ);0.999^(ψψ)

0.999^(ψψ)

1^(ψψ)

1^(ψψ)

1^(ψψ)

0.999^(ψψ)

–

Panther

1629⁽⁺⁺⁾

1629⁽⁺⁺⁾

1629⁽⁺⁺⁾

1238⁽⁺⁺⁾

1237⁽⁺⁺⁾

1238⁽⁺⁺⁾

1237⁽⁺⁺⁾

1629⁽⁺⁺⁾

–

–

–

1038⁽⁺⁺⁾

–

CADD

23.5

23.5

23.5

28.4; 32

28.4; 32

28.5

–

–

–

23.9

–

MAF (GnomAd)

A

A

A

A

A

A

0.00002784

0.00002784

0.000007086

0.00001194

A