Study Of Phenotype And Genetic Characteristics Of Mada Pedigree

PART 1 CLINICAL FEATURES AND MUTATION SCREENING OF PROBAND OF MADAObjective To analyze clinical features of two patients suspected progeria and probable mutation site.Method The medical history and physical examination data of patients was comprehensively collected, laboratory examinations data was collected and some further laboratory examinations were conducted. The informed approvals of institutional review board Chongqing Children’ Hospital of Chongqing Medical University and patients’parents were obtained.Results The two patients suspected progeria had similar clinical features:growth retardation, hair sparse/ alopecia, increased visibility vessels, subcutaneous fat loss, micromandible with crowded teeth, rough skin combined with pigmentation, cleidocranial dysplasia/osteolysis, distal phalanges osteolysis, Type A Lipodystrophy. The results of LMNA gene chip screening showed that the two patients had the same compound heterozygous mutations c.1579C>T (p.Arg527Cys) and c.1583C>T (p.Thr528Met), which might cause MADA.Conclusion Two patients suspected progeria were conformed to the clinical features of Mandibuloacral Dysplasia with Type A Lipodystrophy but not Hutchinson Gilford Progeria Syndrome, Atypical Werner syndrome or Mandibuloacral Dysplasia with Type B Lipodystrophy. The results of LMNA gene chip screening showed compound heterozygous mutations c.1579C>T (p.Arg527Cys) and c.1583C>T (p.Thr528Met) in LMNA gene, which might cause MADA.PART 2 MUTATION SITES VERIFICATION, HEREDITARY FEATURE ANALYSIS AND FOLLOW-UP VISITS IN MADA PEDIGREEObjective To confirm the mutation sites, hereditary feature and follow up the progress of MADA.Method Peripheral venous blood of five family members including parents were collectd, then the Genomic DNA was extracted. The primers of LMNA gene exons were designed, which were used to PCR amplification. The productions of PCR were directly sequenced by S anger method. The results of which were compared by the BLAST tool to further confirm the mutation sites. The harmfulness of mutation sites were analyzed by SIFT and PolyPhen software. Pedigree chart was drawn according to the mutation sites in the family and one-year fellow-up of the patients was conducted.Results There are compoud heterozygous mutations c.1579C>T (p.Arg527Cys) and c.1583C>T (p.Thr528Met) of the LMNA 9th exon in this family, father (c.1583C>T (p.Thr528Met)), mother(c.1579C>T (p.Arg527Cys)) and their daughter(c.1583C>T (p.Thr528Met)) without any progeria symptom are carriers. The compound heterozygous mutation sites of the two patients were confirmed. The harmfulness of the mutation sites was confirmed by SIFT and PolyPhen- software.Conclusion There were two mutation sites which are c.1579C>T (p.Arg527Cys) and c.1583C>T (p.Thr528Met) of the LMNA gene 9th exon in the family, individual with heterozygous mutation site did not show any symptom associated with MADA, but which the patients with compound heterozygous mutations showed. The autosomal recessive inheritance was confirmed in the family.