Ligneous membranitis in Scottish Terriers is associated with a single nucleotide polymorphism in theplasminogen(PLG) gene

Abstract

SummaryLigneous membranitis (LM) is a rare chronic inflammatory condition of the mucous membranes associated with plasminogen (encoded by PLG) deficiency in affected humans and dogs. In human, the condition is genetic in nature with numerous mutations and polymorphisms in PLG identified in affected individuals and related family members. The condition is uncommonly reported in dogs and, to date, no genetic studies have been performed. We identified related Scottish Terriers (littermates) with severe LM and unaffected relatives (sire, dam and a sibling from a previous litter). Plasma plasminogen activity was below normal in one affected dog but within normal reference intervals for the other. Sequencing of PLG from the affected dogs revealed a homozygous A>T single nucleotide polymorphism in an intron donor site (c.1256+2T>A). The related, unaffected dogs displayed heterozygous alleles at this position (c.1256+2T/A), whereas no mutation was detected in unaffected, non‐related control dogs. This is the first report to identify gene polymorphisms associated with LM in dogs.

Presentation, clinical pathological and post‐mortem findings in three related Scottish terriers with ligneous membranitis

“…Hypoplasminogenaemia was not consistently found. Low plasminogen activity was found in only one of two of the affected dogs in which plasma plasminogen was measured but was also noted in an unaffected related dog (Ainsworth et al . 2015 ), which was identified as an offspring of the sire and dam during screening of assumed unrelated Scottish terriers.…”

“…Low plasminogen activity was found in only one of two of the affected dogs in which plasma plasminogen was measured but was also noted in an unaffected related dog (Ainsworth et al . ), which was identified as an offspring of the sire and dam during screening of assumed unrelated Scottish terriers. This situation is also reported in people and may reflect the multiple proteins and pathways involved in fibrinolysis and the development of clinical signs (Tefs et al .…”

“…All unrelated non‐affected controls displayed wild‐type sequences (T/T) (Ainsworth et al . ). This suggests an autosomal recessive pattern of inheritance of the condition in this family of dogs.…”

“…The sire, dam and related controls displayed heterozygous alleles (T/A) at this position. All unrelated non-affected controls displayed wild-type sequences (T/T) (Ainsworth et al . 2015 ).…”

Amniotic membrane transplantation for ligneous conjunctivitis in a doberman

“…Ligneous conjunctivitis (LC) is a rare, distinct form of chronic conjunctivitis that has been described in humans and dogs . The etiology and pathogenesis of LC are incompletely described and poorly understood, but it is suspected to be related to a problem with hypofibrinolysis and has been linked to Type 1 hypoplasminogenemia in humans and some, but not all, canine cases . Grossly, LC is characterized by tough, opaque pseudomembranous lesions that originate from the palpebral conjunctivae and nictitating membranes in the dog.…”