title: Mandibuloacral dysplasia type A-associated progeria caused by homozygous LMNA mutation in a family from Southern China.
abstract: BACKGROUND
  Mandibuloacral dysplasia type A (MADA) is a rare autosomal recessive disorder, characterized by growth retardation, skeletal abnormality with progressive osteolysis of the distal phalanges and clavicles, craniofacial anomalies with mandibular hypoplasia, lipodystrophy and mottled cutaneous pigmentation. Some patients may show progeroid features. MADA with partial lipodystrophy, more marked acral, can be caused by homozygous or compound heterozygous mutation in the gene encoding lamin A and lamin C (LMNA). MADA and Hutchinson-Gilford progeria syndrome are caused by the same gene and may represent a single disorder with varying degrees of severity. MAD patients characterized by generalized lipodystrophy (type B) affecting the face as well as extremities and severe progressive glomerulopathy present heterozygous compound mutations in the ZMPSTE24 gene.
  
  
  METHODS
  We described a rare pedigree from Southern China, among them all three children presented with phenotypes of MADA associated progeria. The two elder sisters had developed severe mandibular hypoplasia associated progeria since the age of 1 year. The eldest sister showed a progressive osteolysis. The youngest son of 10 months showed severer lesions than those of his sisters at the same age, and presented possible muscle damage, and his symptoms progressed gradually. Three genes mutations including LMNA, ZMPSTE24 and BANF1 were tested in the family. LMNA gene sequencing revealed a homozygous missense mutation, c.1579C > T, p.R527C for all three siblings, and heterozygous mutations for their parents, whereas no mutations of ZMPSTE24 and BANF1 genes was detected among them.
  
  
  CONCLUSIONS
  The same homozygous mutation of c.1579C > T of LMNA gene led to MADA associated progeria for the present family. The course of osteolysis for MADA is progressive.
authors.affiliation: Department of Dermatology, The Eastern Hospital of The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510700, China. luodq@mail.sysu.edu.cn.
authors.forename: Di-Qing
authors.initials: DQ
authors.lastname: Luo
authors.forename: Xiao-Zhu
authors.initials: XZ
authors.lastname: Wang
authors.forename: Yan
authors.initials: Y
authors.lastname: Meng
authors.forename: Ding-Yang
authors.initials: DY
authors.lastname: He
authors.forename: Ying-Ming
authors.initials: YM
authors.lastname: Chen
authors.forename: Zhi-Yong
authors.initials: ZY
authors.lastname: Ke
authors.forename: Ming
authors.initials: M
authors.lastname: Yan
authors.forename: Yu
authors.initials: Y
authors.lastname: Huang
authors.forename: Da-Fang
authors.initials: DF
authors.lastname: Chen
mesh_terms: D030981:Acro-Osteolysis / Q000235:genetics*; D044466:Asian People / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D002681:China; D005260:Female; D006720:Homozygote; D006801:Humans; D007223:Infant; D034904:Lamin Type A / Q000235:genetics*; D008060:Lipodystrophy / Q000235:genetics*; D008297:Male; D008334:Mandible / Q000002:abnormalities*; D009154:Mutation; D010014:Osteolysis / Q000235:genetics; D010375:Pedigree; D011371:Progeria / Q000235:genetics*; D035583:Rare Diseases / Q000235:genetics; D035781:Siblings
chemical_list: D034904:Lamin Type A