A novel mutation (g.106737G>T) in zone of polarizing activity regulatory sequence (ZRS) causes variable limb phenotypes in Werner mesomelia.
Werner mesomelia is characterized by a sequence variation in the specific region (position 404) of the enhancer ZRS of SHH. The phenotype comprises variable mesomelia, abnormalities of the thumb and great toe and supernumerary digits. We describe extensive variation in limb phenotype in a large family and report on a novel sequence variation NG_009240.1: g.106737G>T (traditional nomenclature: ZRS404G>T) in the ZRS within the LMBR1 gene. The newly recognized clinical features in this family include small thenar eminence, sandal gap, broad first metatarsals, mesoaxial polydactyly, and postaxial polydactyly. We provide information on 12 affected family members. We review the literature on how a sequence variation in ZRS may cause such diverse phenotypes.
Division of Medical Genetics, Department of Pediatrics, Kasturba Medical College, Manipal University, Manipal, India.
Katta M
KM
Girisha
Abdul Mueed
AM
Bidchol
Preeti S
PS
Kamath
Krupa H
KH
Shah
Geert R
GR
Mortier
Stefan
S
Mundlos
Hitesh
H
Shah
D000328:Adult; D002648:Child; D004742:Enhancer Elements, Genetic; D005121:Extremities; D005260:Female; D006801:Humans; D007223:Infant; D017880:Limb Deformities, Congenital / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D014898:Werner Syndrome / Q000235:genetics*
C485955:LMBR1 protein, human; D008565:Membrane Proteins
five fingered hand; mesoaxial polydactyly; mesomelia; postaxial polydactyly; preaxial polydactyly; small thenar eminence; tibial hemimelia; triphalangeal thumb