Germinal mosaicism for LMNA mimics autosomal recessive congenital muscular dystrophy.
Life-threatening cardiac and respiratory complications are common in LMNA-related myopathies and early diagnosis is important for optimal patient care. Lamin A/C related congenital muscular dystrophy (L-CMD) is often caused by de novo mutation in LMNA, affecting a single child in a family. Germinal mosaicism is a rarer variant that can lead to two children inheriting the same new heterozygous mutation from a clinically unaffected parent. Both patterns mimic autosomal recessive (AR) inheritance and the possibility of de novo L-CMD may be forgotten since most causes of congenital muscular dystrophy follow AR inheritance. To illustrate the challenge of diagnosing L-CMD, we present a consanguineous family in which two children have early onset LMNA-related myopathy likely due to paternal germinal mosaicism. This emphasises that germinal mosaicism (and de novo mutations) for LMNA can arise in any family and direct gene sequencing is required to confirm or exclude the diagnosis.
Makri
Samira
S
Etablissement Hospitalier Spécialisé Ali Ait Idir, Alger, Algeria.
Clarke
Nigel F
NF
Richard
Pascale
P
Maugenre
Svetlana
S
Demay
Laurence
L
Bonne
Gisèle
G
Guicheney
Pascale
P
D000293:Adolescent; D000462:Algeria; D002648:Child; D025063:Chromosome Disorders / Q000235:genetics; D004252:DNA Mutational Analysis; D003937:Diagnosis, Differential; D005260:Female; D005808:Genes, Recessive / Q000235:genetics; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D040582:Inheritance Patterns / Q000235:genetics; D034904:Lamin Type A / Q000235:genetics*; D009030:Mosaicism; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D009135:Muscular Diseases / Q000151:congenital / Q000175:diagnosis* / Q000235:genetics*; D009136:Muscular Dystrophies / Q000175:diagnosis / Q000235:genetics; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D017422:Sequence Analysis, DNA / Q000592:standards
C494847:LMNA protein, human; D034904:Lamin Type A