Mandibuloacral dysplasia and LMNA A529V mutation in Turkish patients with severe skeletal changes and absent breast development.
Mandibuloacral dysplasia (MAD) is an autosomal recessive disorder characterized by acroosteolysis (resorption of terminal phalanges), skin changes (hyperpigmentation), clavicular hypoplasia, craniofascial anomalies, a hook nose and prominent eyes, delayed closures of the cranial sutures, lipodystrophy, alopecia, and skeletal anomalies. MAD patients are classified according to lipodystrophy patterns: type A and type B. The vast majority of MAD cases are caused by LMNA gene mutations. MAD patients with type A lipodystrophy (MADA) have been reported to have LMNA R527H, A529V, or A529T mutations. In this report, we describe two MADA patients with progressive skeletal changes, absent breast development, and cataract in addition to the classical MAD phenotype. Both patients were found to be homozygous for the Ala529Val mutation of the LMNA gene. Our female patient is the oldest MADA patient (59 years old) who has ever been reported with the LMNA mutation and also the LMNA Ala529Val mutation. This study is the second report on MADA patients with a homozygous Ala529Val mutation.
aMikrogen Genetic Diagnosis Center bGen-Art IVF Center cDepartment of Pediatric Genetics, Hacettepe University Faculty of Medicine, Ankara Departments of dHistology and Embryology eMedical Biology and Genetics, Istanbul Bilim University School of Medicine, Istanbul fDepartment of Medical Genetics, Firat University Faculty of Medicine, Elazig, Turkey.
Leyla
L
Ozer
Evrim
E
Unsal
Suleyman
S
Aktuna
Volkan
V
Baltaci
Pelin
P
Celikkol
Fatma
F
Akyigit
Askin
A
Sen
Ozge
O
Ayvaz
Sevim
S
Balci
D030981:Acro-Osteolysis / Q000175:diagnosis* / Q000235:genetics*; D000328:Adult; D019943:Amino Acid Substitution; D003062:Codon; D003241:Consanguinity; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D006720:Homozygote; D006801:Humans; D007621:Karyotyping; D034904:Lamin Type A / Q000235:genetics*; D008060:Lipodystrophy / Q000175:diagnosis* / Q000235:genetics*; D008297:Male; D008334:Mandible / Q000002:abnormalities*; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D014421:Turkey
D003062:Codon; C494847:LMNA protein, human; D034904:Lamin Type A