Combined Mutations of DMD and CFTR Genes in an Azerbaijani Family

Life Sciences-Genetics for Medical Science

Abstract

A  9  year  old  boy  with  the  obvious  traits  of  Duchene  muscular  dystrophy  disease  is  a  resident  of  Masalli  region  of Azerbaijan,  located  in the  south-east  foothill  of Talysh  Mountains.  Family  members  such  as mother,  father  and sister  of this  index patient  were examined. To diagnose all members of the family, biochemical analysis was conducted for quantitative analysis of creatine phosphokinase  in blood serum and genealogical  survey identified  inherited  disease  cystic fibrosis  in first cousin of this index patient  . Quantitative  evaluation  of creatine  phosphokinase  in blood serum was performed  for all family members  of the index patient   ., and identified high values: in index patient (2298 U/L, norm - 38-137 U/L), in his mother (879 U/L, norm - 26-140 U/L) and his sister (852U/L, norm - 26-140 U/L), whereas his father had normal range values of creatine phosphokinase  in blood (53,1 U/L, where norm - 38-137  U/L).  Diagnosis  of Duchenne  muscular  dystrophy  disease  was  confirmed  in index  patient  in hemizygous  state.  His mother  and sister were found as heterozygous  carriers of the (Duchenne  muscular dystrophy)  DMD gene. Molecular  genetic analysis of the DMD gene (MLPA) identified mutation in the mother and sister of the index patient. Mutation type was nonsense, and classified as pathogenic class. Molecular genetic analysis of the DMD gene showed a gain of mutations, consisting of two copies encompassing  exon 03 to 09 in the index patient, mother and his sister. The identified two different mutations of DMD gene in Azerbaijani family: fragment deletion of exon 45 in three sibs from Astara region of Azerbaijan, located in the south-east of the country, and deletion encompassing  exons from 8 to 20 in 10-year-old  boy in Balakan  region,  located  in the north-west  of the Republic  Mutation  type is a nonsense  mutation  and classified as pathogenic of class 1. Inherited cystic fibrosis in heterozygous  state was additionally identified in the index patient, in father and sister. The screening  of identified  mutations  may serve as a prenatal  diagnostic  tool to carefully  plan the prophylaxis  in patients with   cystic fibrosis. Furthermore,  our studies may serve as a basis for the future investigation  of many aberrant molecular mechanisms and regulatory  pathways.  The study of Duchenne  and Becker  muscular  dystrophy  resulted  in one of the first successful  attempts  at reverse genetics, better described as positional cloning, in humans. Discovery and subsequent analysis of the gene mutation that results in the clinical disorder led to the discovery of the encoded protein, dystrophin. This coinage set a precedent for the naming of proteins discovered by positional cloning of human disease genes: for example, huntingtin, emerin, and ataxin