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. Author manuscript; available in PMC: 2018 Jan 1.
Published in final edited form as: Matrix Biol. 2016 Dec 28;57-58:1–11. doi: 10.1016/j.matbio.2016.12.009

Table 1.

Human genetic diseases associated with mutations in basement membrane constituents

Gene Mutation type Mutation effects Disease References
LAMA2 Substitutions, deletions, duplications, insertions, and inversions resulting in protein substitutions, deletions, frame shifts, nonsense, and complex variant Lmα2 chains.

  1. Absent/trace Lmα2 expression functionally null.

  2. Normal/reduced Lmα2 expression seen in single amino acid substitutions and short in- frame deletions in LN and other short arm domains

  1. Absent/trace Lmα2 (most cases): severe non-ambulatory congenital muscular dystrophy with early demise.

  2. Normal/reduced Lmα2 expression: ambulatory (similar to limb-girdle type) muscular dystrophy

 [17]
LAMA3
LAMB3
LAMC2 		Frame shift, nonsense and missense mutations

  1. Premature chain termination.

  2. Missense mutation or putative splicing mutation in trans

 Junctional epidermolysis bullosa (JEB):

  1. Herlitz JEB severe

  2. Non Herlitz JEB milder phenotype

 [19]
LAMB2 Nonsense, missense, spice site mutations, multiple sites. Missense mutations clustered in LN domain.

  1. Truncated and functionally null Lmβ2.

  2. Substitutions: normal/reduced expression of Lmβ2

 Pierson syndrome. Congenital nephrotic syndrome with eye abnormalities, microcoria. Muscular weakness/myasthenia may be present [20]
COL4A1 Frameshift Disruption of the C-terminal NC1 domain Hematuria, chronic kidney disease, renal cysts [21]
COL4A1 G1236R
G749S		 Amino acid change in the triple-helical domain Porencephaly, hemorrhagic strokes [22]
COL4A1 G1769A Amino acid change in the triple-helical domain Retinal hemorrhage, retinopathy [23,24]
COLA4A3
COL4A4
COL4A5 		Splicing variants, missense mutations Altered chain expression Alport syndrome, deafness, lenticonus, cataract, maculopathy [25,26]
COL6A1 Gly missense mutations Amino acid change in the triple helix Ulrich congenital muscular dystrophy: severe hypotonia, early childhood
Bethlehem myopathy: joint laxity and hypotonia		 [27]
COL7A1 Amino acid mutations Loss of α1 chain expression Dystrophic epidermolysis bullosa [28,29]
COL17A1 Missense mutations Exon truncation Epithelial recurrent erosion dystrophy [30,31]
COL17A1 Nonsense mutation Premature stop codons Junctional epidermolysis bullosa [32]
COL18A1 Frame-shift mutations nonsense mutations missense mutations Altered chain reduction
Loss of chain production		 Knobloch syndrome: high myopia, vitroretinal degeneration, occipital encephalocele, fasting triglyceridemia Duplication of kidney collecting system [33–35]
COL18A1 Insertion, frame deletions splice site mutation Change in the C-terminal chain [36]
HSPG2 Duplicated exon 34 and frameshifts Functionally null Dyssegmental dysplasia, Silver-Handmaker type due to altered FGF2 signaling leading to aberrant cartilage architecture [37–39]
HSPG2 Missense and errors in alternative splicing Truncated or ablated Domain V (endorepellin) Schwartz-Jampel syndrome originating from disrupted neuromuscular junction arrangement and function [38,40]
AGRN Missense and nonsense mutations at the N-terminus and LG2 domain Failure of neuromuscular transmission, pre- and post- synaptic Congenital myasthenic syndrome, easy fatigability and muscle weakness [41,42]