Mandibuloacral dysplasia type A in five tunisian patients

Eur J Med Genet. 2021 Feb;64(2):104138. doi: 10.1016/j.ejmg.2021.104138. Epub 2021 Jan 8.

Abstract

Mandibuloacral dysplasia with type A lipodystrophy is a rare autosomal recessive disorder characterized by craniofacial dysmorphism, type A lipodystrophy, clavicular dysplasia, and acroostelolysis. It is caused by homozygous or compound heterozygous missense mutations in LMNA gene. We report five Tunisian patients harboring the same homozygous c.1580G > A; p. (Arg527His) mutation in LMNA gene. The patients presented with typical features of mandibuloacral dysplasia including, prominent eyes, thin or beaked nose, dental overcrowding, mandibular hypoplasia, short and broad finger's distal phalanges with round tips and lipodystrophy type A. Newly recognized signs are growth hormone deficiency and dilated cardiomyopathy. Genotype-phenotype correlation found that at least one of the disease's LMNA mutant alleles involve one of the highly conserved aminoacids, residing in a key site domain for protein function within the C-terminal globular domain of A-type lamins. Also, the severity of the disease depends on the position in the protein's domain and on the type of substitution of the concerned aminoacid.

Keywords: Cardiomyopathy; Growth hormone; LMNA; Mandibuloacral dysplasia with type a lipodystrophy; Tunisia.

Publication types

  • Case Reports

MeSH terms

  • Acro-Osteolysis / genetics*
  • Acro-Osteolysis / pathology
  • Adolescent
  • Child
  • Female
  • Humans
  • Lamin Type A / chemistry
  • Lamin Type A / genetics*
  • Lipodystrophy / genetics*
  • Lipodystrophy / pathology
  • Male
  • Mandible / abnormalities*
  • Mandible / pathology
  • Mutation, Missense
  • Pedigree
  • Phenotype
  • Protein Domains

Substances

  • LMNA protein, human
  • Lamin Type A

Supplementary concepts

  • Mandibuloacral dysplasia with type A lipodystrophy