Mutation detection in activin A receptor, type I [ACVR1] gene in fibrodysplasia ossificans progressiva in an iranian family

Fibrodysplasia Ossificans Progressiva [FOP, MIM 135100] is a rare genetic disease that is often inherited sporadically in an autosomal dominant pattern. The disease manifests in early life with malformed great toes and, its episodic and progressive bone formation in skeletal muscle after trauma is led to extra-articular ankylosis. In this study, a 17 year-old affected girl born to a father with chemical injury due to exposure to Mustard gas during the Iran-Iraq war, and her first degree relatives were examined to find the genetic cause of the disease. The mutation c.617G>A in the Activin A receptor, type I [ACVR1] gene was found in all previously reported patients with FOP. Therefore, peripheral blood samples were taken from the patient and her first-degree relatives. DNA was extracted and PCR amplification for ACVR1 was performed. The sequencing of ACVR1 showed the existence of the heterozygous c.617G>A mutation in the patient and the lack of it in her relatives. Normal result of genetic evaluation in relatives of the patient, ruled out the possibility of the mutation being inherited from parents. Therefore, the mutation causing disease in the child, whether is a new mutation with no relation to the father's exposure to chemical gas, or in case of somatic mutation due to exposure to chemical gas, the mutant cells were created in father's germ cells and were not detectable in his blood sample

Detecting rare triple heteroplasmic substitutions in the mitochondrial DNA control region: a potential concern for forensic DNA studies

Mitochondrial DNA [mtDNA] is a useful tool for population studies, identification of humans and forensic DNA studies. The existence of several hundreds copies of mtDNA per cell permit its extraction from minute or degraded samples. In addition, the level of polymorphism in the hypervariable [HV] region is high enough to permit its use in human identity testing. However, the presence of several heteroplasmy might lead to ambiguous results. This study was an experiental study. This study evaluated heteroplasmy in the HV region of mtDNA in blood samples of 30 Iranians who belonged to ten unrelated families from three sequential generations [grandmother, mother and daughter]. There were no heteroplasmic substitutions in the HV1 region, but analysis of HV2 showed heteroplasmic substitutions in two out ten families. In the first family the grandmother showed heteroplasmy [T/C] in nucleotide positions 146 and 151, however it was not detected in the mother and daughter. In second family, a triple heteroplasmy [T/C] was detected in the daughter in nucleotide positions 146, 151 and 295, but these heteroplasmic substitutions were not obvious in the grandmother and mother. Heteroplasmy in mtDNA is not a rare phenomenon and probably exists in everyone, but a triple heteroplasmy in one family member is a novel finding. Our results demonstrate that one or two sequence differences between samples in mtDNA do not warrant exclusion. In our study, the average nucleotide difference between unrelated persons in the HV2 region was 2.8 nucleotides, whereas there was a triple heteroplasmy in one person which was not obvious in her family