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Three Novel Heterozygous COL4A4 Mutations Result in Three Different Collagen Type IV Kidney Disease Phenotypes.

Abstract Thin basement membrane nephropathy (TBMN), autosomal dominant Alport syndrome (ADAS), and focal segmental glomerulosclerosis (FSGS) are kidney diseases that differ in clinical diagnosis, treatment, and prognosis. Nevertheless, they may result from the same causative genes. Here, we report 3 COL4A4 heterozygous mutations (p.Gly208Arg, p.Ser513Glufs*2, and p.Met1617Cysfs*39) that lead to 3 different collagen type IV kidney disease phenotypes, manifesting as TBMN, ADAS, and FSGS. Using bioinformatics analyses and pedigree verification, we show that these novel variants are pathogenetic and cosegregate with TBMN, ADAS, and FSGS. Furthermore, we found that the collagen type IV-associated kidney disease phenotypes are heterogeneous, with overlapping pathology and genetic mutations. We propose that COL4A4-associated TBMN, ADAS, and FSGS should be considered as collagen type IV kidney disease subtypes that represent different phases of disease progression.
PMID
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Authors

Mayor MeshTerms

Mutation

Keywords

<italic>COL4A4</italic> mutations

Autosomal dominant Alport syndrome

Collagen type IV kidney disease

Focal segmental glomerulosclerosis

Thin basement membrane nephropathy

Journal Title cytogenetic and genome research
Publication Year Start




PMID- 29669314
OWN - NLM
STAT- MEDLINE
DCOM- 20180430
LR  - 20180430
IS  - 1424-859X (Electronic)
IS  - 1424-8581 (Linking)
VI  - 154
IP  - 1
DP  - 2018
TI  - Three Novel Heterozygous COL4A4 Mutations Result in Three Different Collagen Type
      IV Kidney Disease Phenotypes.
PG  - 30-36
LID - 10.1159/000486979 [doi]
AB  - Thin basement membrane nephropathy (TBMN), autosomal dominant Alport syndrome
      (ADAS), and focal segmental glomerulosclerosis (FSGS) are kidney diseases that
      differ in clinical diagnosis, treatment, and prognosis. Nevertheless, they may
      result from the same causative genes. Here, we report 3 COL4A4 heterozygous
      mutations (p.Gly208Arg, p.Ser513Glufs*2, and p.Met1617Cysfs*39) that lead to 3
      different collagen type IV kidney disease phenotypes, manifesting as TBMN, ADAS, 
      and FSGS. Using bioinformatics analyses and pedigree verification, we show that
      these novel variants are pathogenetic and cosegregate with TBMN, ADAS, and FSGS. 
      Furthermore, we found that the collagen type IV-associated kidney disease
      phenotypes are heterogeneous, with overlapping pathology and genetic mutations.
      We propose that COL4A4-associated TBMN, ADAS, and FSGS should be considered as
      collagen type IV kidney disease subtypes that represent different phases of
      disease progression.
CI  - (c) 2018 S. Karger AG, Basel.
FAU - Li, Ang
AU  - Li A
AD  - Institute of Clinical Laboratory Science, Jinling Hospital, Nanjing University
      School of Medicine, Nanjing, China.
FAU - Gao, Er-Zhi
AU  - Gao EZ
FAU - Cui, Ying-Xia
AU  - Cui YX
FAU - Liu, Jian-Hong
AU  - Liu JH
FAU - Lv, Xing
AU  - Lv X
FAU - Wei, Xiu-Xiu
AU  - Wei XX
FAU - Xia, Xin-Yi
AU  - Xia XY
FAU - Gao, Chun-Lin
AU  - Gao CL
FAU - Liu, Feng-Xia
AU  - Liu FX
FAU - Xia, Zheng-Kun
AU  - Xia ZK
FAU - Asan
AU  - Asan
FAU - Liu, Zhi-Hong
AU  - Liu ZH
FAU - Li, Xiao-Jun
AU  - Li XJ
LA  - eng
PT  - Case Reports
PT  - Journal Article
DEP - 20180215
PL  - Switzerland
TA  - Cytogenet Genome Res
JT  - Cytogenetic and genome research
JID - 101142708
RN  - 0 (COL4A4 protein, human)
RN  - 0 (Collagen Type IV)
RN  - Hematuria, Benign Familial
SB  - IM
MH  - Adult
MH  - Child
MH  - Collagen Type IV/*genetics/metabolism
MH  - DNA Mutational Analysis
MH  - Glomerular Basement Membrane/metabolism/pathology/ultrastructure
MH  - Glomerulosclerosis, Focal Segmental/*genetics/metabolism
MH  - Hematuria/*genetics/metabolism
MH  - Heterozygote
MH  - Humans
MH  - Male
MH  - Microscopy, Electron
MH  - *Mutation
MH  - Nephritis, Hereditary/*genetics/metabolism
MH  - Phenotype
OTO - NOTNLM
OT  - &lt;italic&gt;COL4A4&lt;/italic&gt; mutations
OT  - Autosomal dominant Alport syndrome
OT  - Collagen type IV kidney disease
OT  - Focal segmental glomerulosclerosis
OT  - Thin basement membrane nephropathy
EDAT- 2018/04/19 06:00
MHDA- 2018/05/01 06:00
CRDT- 2018/04/19 06:00
PHST- 2017/11/22 00:00 [accepted]
PHST- 2018/04/19 06:00 [entrez]
PHST- 2018/04/19 06:00 [pubmed]
PHST- 2018/05/01 06:00 [medline]
AID - 000486979 [pii]
AID - 10.1159/000486979 [doi]
PST - ppublish
SO  - Cytogenet Genome Res. 2018;154(1):30-36. doi: 10.1159/000486979. Epub 2018 Feb
      15.