title: Cenani-Lenz syndrome restricted to limb and kidney anomalies associated with a novel LRP4 missense mutation.
abstract: Cenani-Lenz syndrome (CLS) is a rare autosomal recessive developmental disorder of the limbs. The disorder is characterized by complete syndactyly with metacarpal fusions and/or oligodactyly sometimes accompanied by radioulnar synostosis. The clinical expression is variable and kidney agenesis/hypoplasia, craniofacial dysmorphism and teeth abnormalities are frequent features as well as lower limb involvement. CLS was recently associated with mutations in the low-density lipoprotein receptor-related protein 4 (LRP4) gene and dysregulated canonical WNT signaling. We have identified a large consanguineous Pakistani pedigree with 9 members affected by CLS. The affected individuals present with a consistent expression of the syndrome restricted to the limbs and kidneys. Symptoms from the lower limb are mild or absent and there were no radioulnar synostosis or craniofacial involvement. Genetic analysis using autozygosity mapping and sequencing revealed homozygosity for a novel missense mutation c.2858T > C (p.L953P) in the LRP4 gene. The mutation is located in a region encoding the highly conserved low-density lipoprotein receptor repeat class B domain of LRP4. Our findings add to the genotype-phenotype correlations in CLS and support kidney anomalies as a frequent associated feature.
authors.affiliation: Human Molecular Genetics Laboratory, Health Biotechnology Division, National Institute for Biotechnology and Genetic Engineering (NIBGE), 38000 Faisalabad, Pakistan.
authors.forename: Tahir Naeem
authors.initials: TN
authors.lastname: Khan
authors.forename: J
authors.initials: J
authors.lastname: Klar
authors.forename: Zafar
authors.initials: Z
authors.lastname: Ali
authors.forename: F
authors.initials: F
authors.lastname: Khan
authors.forename: S M
authors.initials: SM
authors.lastname: Baig
authors.forename: N
authors.initials: N
authors.lastname: Dahl
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D002648:Child; D005260:Female; D006720:Homozygote; D006801:Humans; D007668:Kidney / Q000002:abnormalities*; D026502:LDL-Receptor Related Proteins / Q000235:genetics*; D038061:Lower Extremity Deformities, Congenital / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010375:Pedigree; D013576:Syndactyly / Q000175:diagnosis / Q000235:genetics*
chemical_list: D026502:LDL-Receptor Related Proteins; C551781:LRP4 protein, human
keywords: Cenani–Lenz syndrome; Clinical expression; LRP4; Mutation