Analysis Of Phenotype In Two Patients With Laminopathies And LMNA Gene

Background and ObjectiveLaminopathies is a kind of rare human heredopathia caused by mutations in the LMNA gene and defect in the laminA/C protein.The disease has three characteristics: involved tissues derived from mesoderm;feature of dysplasia or degenerative;caused by mutations of LMNA gene and defect of laminA/C.Now,more than10clearly defined phenotypes have been reported to associate with LMNA gene mutation.LMNA gene encodes the laminA and laminC which are key components of the nuclear lamina by utilization of an alternative splice site in exon l0.This study was mainly to analysis phenotype of two cases and explore wheather there are mutation within the12th exons in LMNA gene.The objective is going to confirme diagnosis and classification.Subjects and MethodTwo patients with laminopathies have been diagnosed and treated in our department in the past.Genomic DNA was collected from the blood samples of two patients and their parents. lth-12th exons were detected by PCR and direct sequencing. Resultsl.The first patient was clinically diagnosed as a novel laminopathy which manifested as an overlapping phenotype among Mandibuloacral dysplasia, Familial Partial Lipodystrophy, Progeroid Features, Deafness and Hypogonadism. No mutations of the12exons in the LMNA gene was detected in the patient and her parents;2. The second patient was clinically diagnosed as pubertal-onset generalized lipodystrophy. A heterozygous CGG to CTG transversion was found at LMNA gene codon133.This mutation lead to an arginine to leucine sudstitution.His father was wide-type.Conclusionl.The first patient have a few overlapping but some distinct clinical features,suggesting that it is a novel laminopathies.The molecular basis remains to be elucidated.2. The heterozygous CGG to CTG transversion at codon133in exon2of LMNA gene in the second patient contributes to pubertal-onset generalized lipodystrophy.