@article {970,
	title = {A mutation affecting laminin alpha 5 polymerisation gives rise to a syndromic developmental disorder.},
	journal = {Development},
	volume = {147},
	year = {2020},
	month = {2020 06 22},
	abstract = {<p>Laminin alpha 5 (LAMA5) is a member of a large family of proteins that trimerise and then polymerise to form a central component of all basement membranes. Consequently, the protein plays an instrumental role in shaping the normal development of the kidney, skin, neural tube, lung and limb, and many other organs and tissues. Pathogenic mutations in some laminins have been shown to cause a range of largely syndromic conditions affecting the competency of the basement membranes to which they contribute. We report the identification of a mutation in the polymerisation domain of LAMA5 in a patient with a complex syndromic disease characterised by defects in kidney, craniofacial and limb development, and by a range of other congenital defects. Using CRISPR-generated mouse models and biochemical assays, we demonstrate the pathogenicity of this variant, showing that the change results in a failure of the polymerisation of α/β/γ laminin trimers. Comparing these  phenotypes with those apparent upon gene deletion in mice provides insights into the specific functional importance of laminin polymerisation during development and tissue homeostasis.</p>},
	keywords = {Amino Acid Sequence, Animals, Animals, Newborn, Child, Preschool, Developmental Disabilities, Fetal Development, Fetus, Humans, Hydronephrosis, Infant, Newborn, Kidney, Laminin, Lung, Male, Mice, Mutation, Polymerization, Protein Domains, Syndrome},
	issn = {1477-9129},
	doi = {10.1242/dev.189183},
	author = {Jones, Lynelle K and Lam, Rachel and McKee, Karen K and Aleksandrova, Maya and Dowling, John and Alexander, Stephen I and Mallawaarachchi, Amali and Cottle, Denny L and Short, Kieran M and Pais, Lynn and Miner, Jeffery H and Mallett, Andrew J and Simons, Cas and McCarthy, Hugh and Yurchenco, Peter D and Smyth, Ian M}
}
@article {432,
	title = {Nemaline myopathy and distal arthrogryposis associated with an autosomal recessive~TNNT3~splice variant.},
	journal = {Hum Mutat},
	volume = {39},
	year = {2018},
	month = {2018 03},
	pages = {383-388},
	abstract = {<p>A male neonate presented with severe weakness, hypotonia, contractures and congenital scoliosis. Skeletal muscle specimens showed marked atrophy and degeneration of fast fibers with striking nemaline rods and hypertrophy of slow fibers that were ultrastructurally normal. A neuromuscular gene panel identified a homozygous essential splice variant in TNNT3 (chr11:1956150G~>~A, NM_006757.3:c.681+1G~>~A). TNNT3 encodes skeletal troponin-T and is associated with autosomal dominant distal arthrogryposis. TNNT3 has not previously been associated with nemaline myopathy (NM), a rare congenital myopathy linked to defects in proteins associated with thin filament structure and regulation. cDNA studies confirmed pathogenic consequences of the splice variant, eliciting exon-skipping and intron retention events leading to a frameshift. Western blot showed deficiency of troponin-T protein with secondary loss of troponin-I . We establish a homozygous splice variant in TNNT3 as the likely cause of severe congenital NM with distal arthrogryposis, characterized by specific involvement of Type-2 fibers and deficiency of troponin-T .</p>},
	keywords = {Arthrogryposis, Genes, Recessive, Humans, Infant, Infant, Newborn, Male, Myopathies, Nemaline, RNA Splice Sites, RNA Splicing, RNA, Messenger, Troponin T},
	issn = {1098-1004},
	doi = {10.1002/humu.23385},
	author = {Sandaradura, Sarah A and Bournazos, Adam and Mallawaarachchi, Amali and Cummings, Beryl B and Waddell, Leigh B and Jones, Kristi J and Troedson, Christopher and Sudarsanam, Annapurna and Nash, Benjamin M and Peters, Gregory B and Algar, Elizabeth M and MacArthur, Daniel G and North, Kathryn N and Brammah, Susan and Charlton, Amanda and Laing, Nigel G and Wilson, Meredith J and Davis, Mark R and Cooper, Sandra T}
}
