Linkage Study Revealed Complex Haplotypes in a Multifamily due to Different Mutations in CAPN3 Gene in an Iranian Ethnic Group.
Calpainopathy is an autosomal recessive form of limb girdle muscular dystrophies which is caused by mutation in CAPN3 gene. In the present study, co-segregation of this disorder was analyzed with four short tandem repeat markers linked to the CAPN3 gene. Three apparently unrelated Iranian families with same ethnicity were investigated. Haplotype analysis and sequencing of the CAPN3 gene were performed. DNA sample from one of the patients was simultaneously sent for next-generation sequencing. DNA sequencing identified two mutations. It was seen as a homozygous c.2105C>T in exon 19 in one family, a homozygous novel mutation c.380G>A in exon 3 in another family, and a compound heterozygote form of these two mutations in the third family. Next-generation sequencing also confirmed our results. It was expected that, due to the rare nature of limb girdle muscular dystrophies, affected individuals from the same ethnic group share similar mutations. Haplotype analysis showed two different homozygote patterns in two families, yet a compound heterozygote pattern in the third family as seen in the mutation analysis. This study shows that haplotype analysis would help in determining presence of different founders.
Department of Molecular Medicine, Biotechnology Research Center, Pasteur Institute of Iran, Pasteur St., Tehran, Iran.|Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Marzieh
M
Mojbafan
Pediatric Neurology Center of Excellence, Department of Pediatric Neurology, Mofid Children Hospital, Faculty of Medicine, Shahid Beheshti Medical University, Tehran, Iran.
Seyed Hassan
SH
Tonekaboni
Department of Molecular Medicine, Biotechnology Research Center, Pasteur Institute of Iran, Pasteur St., Tehran, Iran.|Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Maryam
M
Abiri
Medical Genetics Laboratory, Kawsar Human Genetics Research Center (KHGRC), No. 41 Majlesi St., Valiasr St., Tehran, Iran, 1595645513.
Soudeh
S
Kianfar
Medical Genetics Laboratory, Kawsar Human Genetics Research Center (KHGRC), No. 41 Majlesi St., Valiasr St., Tehran, Iran, 1595645513.
Ameneh
A
Sarhadi
Pediatric Pathology Research Center, Mofid Children's Hospital, Shahid Beheshti Medical University (SBMU), Tehran, Iran.
Yalda
Y
Nilipour
Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Javad
J
Tavakkoly-Bazzaz
Department of Molecular Medicine, Biotechnology Research Center, Pasteur Institute of Iran, Pasteur St., Tehran, Iran. zeinali@kawsar.ir.|Medical Genetics Laboratory, Kawsar Human Genetics Research Center (KHGRC), No. 41 Majlesi St., Valiasr St., Tehran, Iran, 1595645513. zeinali@kawsar.ir.
Sirous
S
Zeinali
D000293:Adolescent; D002154:Calpain / Q000235:genetics*; D002648:Child; D005091:Exons; D005260:Female; D006239:Haplotypes; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007492:Iran; D008297:Male; D018895:Microsatellite Repeats; D009124:Muscle Proteins / Q000235:genetics*; D049288:Muscular Dystrophies, Limb-Girdle / Q000208:ethnology / Q000235:genetics*; D009154:Mutation; D010375:Pedigree; D055815:Young Adult
D009124:Muscle Proteins; C105884:CAPN3 protein, human; D002154:Calpain
Autozygosity mapping; Compound heterozygote; Ethnicity; Limb girdle muscular dystrophy; Short tandem repeat