Combined Mutations of DMD and CFTR Genes in an Azerbaijani Family

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 (852 U/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.