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Table 5 Genetic characteristics of patients with inherited tubulointerstitial kidney disease in the present study

From: Prevalence of inherited changes of uric acid levels in kidney dysfunction including stage 5 D and T: a systematic review

Case

Status

Pathogenic factor (s) for clinical relevance

Mutation gene

Nucleotide change

Effect on coding sequence (a.a change)

Region (exon)

Type of inheritance

Race/ethnicity

Ref

Proband 1

HTZ missense

Proline residue, high mature: precursor ratio of uromodulin protein

UMOD

c.C518G

p.P173R

4

AD

Japan

[10]

Proband 2

HTZ missense

Altered evolutionary conserved residues in encoding UMOD gene

UMOD

c.187T>C

p.Cys63Arg

3

AD

Korea

[11]

Proband 3

HTZ missense

Co-segregation with disease, altered cysteine residue of uromodulin

UMOD

c.1382C>A

p.Ala461Glu

6

AD

Korea

[12]

Proband 4

HTZ missense

Co-segregation of disease phenotypes

UMOD

c0.667 TG

G, p.223, Cysteine

3

AD

China

[19]

Proband 5

missense

Ca-binding EGF-like domains of uromodulin protein

UMOD

c.189C > G

C63W

4

AD

Turkey

[20]

Proband 6

HTZ missense

Mutation in UMOD encoding uromodulin protein (THP)

UMOD

c.920A → C

p.K307 T

5

AD

Portugal

[21]

Proband 7

Sequence variant

Loss of a cysteine residue in the EGF domain of uromodulin protein

UMOD

c (0).2297> C

Cys77Arg

4

AD

Poland

[24]

Proband 8

HTZ substitution

Aminoacid substitution

UMOD

T403G

c.135G

4

AD

Japan

[25]

Proband 9

Homo nonsense

Aminoacid substitution

UMOD

c.589G>T

p.E197X

3

AD

Iran

[26]

Proband 10

HTZ missense

Altered evolutionary conserved residues in encoding UMOD gene

UMOD

c.688T>C

p. Trp 230Arg

4

AD

Japan

[27]

Proband 11

No gene mutation identified

No causal gene identified, new monogenic cause

UMOD, REN, HNF1β-negative

–

–

–

AD

UK

[28]

Proband 12

HTZ transversion mutation

Aminoacid substitution and significant conformational change

UMOD

c.891T>G

p.C297W

4

AD

Hungary

[29]

Proband 13

HTZ transversion mutation

Aminoacid substitution and significant conformational change

UMOD

c.891T>G

p.C297W

4

AD

Hungary

[29]

Proband 14

HTZ transversion mutation

Aminoacid substitution and significant conformational change

UMOD

c.891T>G

p.C297W

4

AD

Hungary

[29]

Proband 15

HTZ transversion mutation

Aminoacid substitution and significant conformational change

UMOD

c.891T>G

p.C297W

4

AD

Hungary

[29]

Proband 16

missense mutation

1. Conserved cysteine to glycine aminoacid substitution in uromodulin zona pollucida domain

2. Delay protein export to the PM due to insertion in ER

3. Uromodulin deficiency

4. Co-segregation

UMOD

c.1039T>G

p.C347G

6

AD

Berlin

[32]

Proband 17

Missense mutation

1. conserved cysteine to glycine aminoacid substitution in uromodulin zona pollucida domain

2. delay protein export to the PM due to insertion in ER

3. Uromodulin

Deficiency

4. Co-segregation

UMOD

1039T>G

p.C347G

6

AD

Berlin

[32]

Proband 18

HTZ

1. Co-segregation

UMOD

C744G

Cys248Trp

6

AD

Italy

[33]

Proband 19

HTZ

1.Reduction of urinary excretion of UMOD

2. Co-segregation

UMOD

C744G

Cys248Trp

4

AD

Turkey

[33]

Proband 20

HTZ

Co-segregation

UMOD

C744G

Cys248Trp

4

AD

German

[33]

Proband 21

HTZ

Reduction of urinary excretion of UMOD

UMOD

C744G

Cys248Trp

4

AD

Switzerland

[33]

Proband 22

HTZ

1. Highly conserved of the cysteine residues in the UMOD protein throughout evolution

2. Co-segregation

UMOD

T229G

Cys77Gly

4

AD

USA

[33]

Proband 23

HTZ missense

1. Altered disulfide bond formation due to substitution, retention in ER leading to unfolded protein response and apoptosis

2. Highly conserved of the cysteine residues in the UMOD protein throughout evolution

3. Co-segregation

UMOD

c.949T>G

p.C317G

5

AD

India

[38]

Proband 24

HTZ missense

1. Altered disulfide bond formation due to substitution, retention in ER leading to unfolded protein response and apoptosis

2. Highly conserved of the cysteine residues in the UMOD protein throughout evolution

3. Co-segregation

UMOD

c.949T>G

p.C317G

5

AD

India

[38]

Proband 25

HTZ missense

Mutation in EGF1 domain, misfolding of the UMOD protein

UMOD

c.163G>A

p.Gly55Ser

4

AD

Brazil

[42]

Proband 26

–

–

UMOD

–

–

–

AD

USA

[43]

Proband 27

Homozyous missense

–

UMOD

c.263G>A

p.Gly88Asp

–

AR

Turkey

[44]

Proband 28

HTZ missense

ZP domain of uromodulin protein

UMOD

c.1648G>A

p.V550I

8

AD

China

[45]

Proband 29

–

–

UMOD

c.517G>A

p.proP173Ala

3

AD

Spain

[46]

Probands 30

HTZ

Protein deposits of misfolded uromodulin leading to misfolded protein accumulation in ER and ER stress, absence of uromodulin in apical membranes

UMOD

c.707C>G

p.pro236Arg

3

AD

Caucasian

[47]

Proband 31

HTZ missense

1. Accumulation of uromodulin into ER

2. Maturation impairement

3. Severe reduction of uromodulin excretion

UMOD

c.C317Y

950G>A

5

AD

Italy

[48]

Proband 32

HTZ missense

1. Accumulation of uromodulin into ER

2. Maturation impairement

3. Severe reduction of uromodulin excretion

UMOD

c.C317Y

950G>A

5

AD

Italy

[48]

Proband 33

HTZ missense

1. Accumulation of uromodulin into ER

2. Maturation impairement

3. Severe reduction of uromodulin excretion

UMOD

c.C317Y

950G>A

5

AD

Italy

[48]

Proband 34

HTZ missense

1. Accumulation of uromodulin into ER

2. Maturation impairement

3. Severe reduction of uromodulin excretion

UMOD

c.C317Y

950G>A

5

AD

Italy

[48]

Proband 35

HTZ missense

1. Accumulation of uromodulin into ER

2. Maturation impairement

3. Severe reduction of uromodulin excretion

UMOD

c.C317Y

950G>A

5

AD

Italy

[48]

Proband 36

HTZ missense

1. Accumulation of uromodulin into ER

2. Maturation impairement

3. Severe reduction of uromodulin excretion

UMOD

c.C317Y

950G>A

5

AD

Italy

[48]

Proband 37

HTZ missense

1. Accumulation of uromodulin into ER

2. Maturation impairement

3. Severe reduction of uromodulin excretion

UMOD

c.C317Y

950G>A

5

AD

Italy

[48]

Proband 38

HTZ missense

1. Accumulation of uromodulin into ER

2. Maturation impairement

3. Severe reduction of uromodulin excretion

UMOD

c.C315R

943T>C

5

AD

Italy

[48]

Proband 39

HTZ missense

1. Accumulation of uromodulin into ER

2. Maturation impairement

3. Severe reduction of uromodulin excretion

UMOD

c.C315R

943T>C

5

AD

Italy

[48]

Proband 40

HTZ missense

1. Accumulation of uromodulin into ER

2. Maturation impairement

3. Severe reduction of uromodulin excretion

UMOD

c.C315R

943T>C

5

AD

Italy

[48]

  1. AD autosomal dominance, ER endoplasmic reticulum, HTZ heterozygous, PM plasma membrane, UMOD uromodulin