Medical College of Wisconsin
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Mutations in LAMA1 cause cerebellar dysplasia and cysts with and without retinal dystrophy. Am J Hum Genet 2014 Aug 07;95(2):227-34 PMID: 25105227 PMCID: PMC4129402

Pubmed ID





Cerebellar dysplasia with cysts (CDC) is an imaging finding typically seen in combination with cobblestone cortex and congenital muscular dystrophy in individuals with dystroglycanopathies. More recently, CDC was reported in seven children without neuromuscular involvement (Poretti-Boltshauser syndrome). Using a combination of homozygosity mapping and whole-exome sequencing, we identified biallelic mutations in LAMA1 as the cause of CDC in seven affected individuals (from five families) independent from those included in the phenotypic description of Poretti-Boltshauser syndrome. Most of these individuals also have high myopia, and some have retinal dystrophy and patchy increased T2-weighted fluid-attenuated inversion recovery (T2/FLAIR) signal in cortical white matter. In one additional family, we identified two siblings who have truncating LAMA1 mutations in combination with retinal dystrophy and mild cerebellar dysplasia without cysts, indicating that cysts are not an obligate feature associated with loss of LAMA1 function. This work expands the phenotypic spectrum associated with the lamininopathy disorders and highlights the tissue-specific roles played by different laminin-encoding genes.

Author List

Aldinger KA, Mosca SJ, T├ętreault M, Dempsey JC, Ishak GE, Hartley T, Phelps IG, Lamont RE, O'Day DR, Basel D, Gripp KW, Baker L, Stephan MJ, Bernier FP, Boycott KM, Majewski J, University of Washington Center for Mendelian Genomics, Care4Rare Canada, Parboosingh JS, Innes AM, Doherty D


Donald Basel MD Chief, Associate Professor in the Pediatrics department at Medical College of Wisconsin


2-s2.0-84905816192   38 Citations

MESH terms used to index this publication - Major topics in bold

Base Sequence
Cerebellar Cortex
Cerebellar Diseases
Child, Preschool
Muscular Dystrophies
Retinal Dystrophies
Sequence Analysis, DNA
Young Adult
jenkins-FCD Prod-321 98992d628744e349846c2f62ac68f241d7e1ea70