Prevalence of alpha-1-antitrypsin gene mutations in Saudi Arabia

alpha-1 antitrypsin [AAT] deficiency results from mutations of the protease inhibitor [PI]. The AAT gene is mapped on chromosome 14 and has been associated with chronic liver disease and chronic obstructive pulmonary disease [COPD]. To determine the frequency of AAT mutations on S and Z carrier alleles in healthy Saudi individuals from Qassim Province in Saudi Arabia. A total of 158 healthy, unrelated participants from Qassim Province were recruited. They were genotyped for the two AAT-deficiency alleles, PI*S and PI*Z, using polymerase chain reaction, with primers designed throughout to mediate site-directed mutagenesis. Of the 158 subjects, 11.39% were carriers for the S mutation [i.e., had the MS genotype], whereas 2.53% were carriers for the Z mutation [i.e., had the MZ genotype]. The SZ genotype was present in 3.8% of subjects, while the homozygous genotype SS was present in 1.9% of subjects. No subjects showed the ZZ mutant genotype. Accordingly, frequency of the mutant S and Z alleles of AAT gene was 9.49% and 3.19%, respectively. The results obtained showed a high prevalence of the AAT deficiency allele in the Saudi population. This probably warrants adoption of a screening program for at-risk individuals, so that they might initiate adequate prophylactic measures

Diagnosis of sex chromosome disorders and prenatal diagnosis of Down Syndrome using interphase Fluorescent In-Situ Hyperidization Technique

Background: Thousands of infants are born each year with chromosomal abnormalities that severely impact physical and mental development. Among common genetic disorders are Down syndrome [trisomy 21] and sex chromosomal disorders

Objectives: Evaluation of guidelines used for prenatal diagnosis of Down syndrome [DS] as well as sex chromosomal disorders including interphase Fluorescent In Situ Hyperidization [FISH] technique

Methods: Enrolled cases were among those presenting to Genetics and Neonatology Units, Mansoura and Ain-Shams University hospitals,[Egypt] during 2002 to 2004. These included: Groups 1 comprised fifty pregnant women presenting for genetic counseling. They were subjected to complete history analysis, ultrasound examination in addition to triple screening test [for alpha feto protein [AFP], human chorionic goandotrophin [HCG] and unconjugated esteriol [E2]. Results were confirmed by doing routine karyogram on cultured amniotic fluid. Groups 2 comprised suspected cases with sex chromosomal disorders including neonates with ambiguous genitalia [64 cases] and adults with primary amenorrhea [69 cases] or infertility [38 cases]. They were subjected to a diagnostic workup including

Results: Among the pregnant women group, seven were found to be at a high risk of having DS fetuses including 3 cases with a history of affected off-springs, 2 cases with age above 35 years, and 2 cases with high triple test. Only one case had positive trisomy 21 on interphase FISH confirmed by karyogram on cultured amniotic cells. The other 6 ladies had normal FISH confirmed by karyograms. Regarding the other group, 5 cases out of the 9 females were proved to be feminized males, one proved mosaic turner, one proved mixed gonadal dysgenesis and 2 normal females. On the other hand one out of three males were proved to be verilized female while the other one was a male with incomplete testicular feminization and the last one was a male with infertility diagnosed as Klinefelter syndrome at the age of 26 years

Conclusion: Interphase FISH is a rapid, accurate and very sensitive method in sex chromosom and autosomal abnormalities. It adds to the diagnostic utility of routine cytogenetics and its use on interphase nuclei overcomes the difficulty of conventional cytogenetics. It could be used in the prenatal diagnosis of DS in addition to ultrasonography, and triple test

Diagnosis of sex chromosome disorders and prenatal diagnosis of Down syndrome using interphase fluorescent in-situ hyperidization technique

Thousands of infants are born each year with chromosomal abnormalities that severely impact physical and mental development. Among common genetic disorders are Down syndrome [trisomy 21] and sex chromosomal disorders. Evaluation of guidelines used for prenatal diagnosis of Down syndrome [DS] as well as sex chromosomal disorders including interphase Fluorescent In Situ Hyperidization [FISH] technique. Enrolled cases were among those presenting to Genetics and Neonatology Units, Mansoura and Ain-Shams University hospitals,[Egypt] during 2002 to 2004. These included: Groups 1 comprised fifty pregnant women presenting for genetic counseling. They were subjected to complete history analysis, ultrasound examination in addition to triple screening test [for alpha feto protein [AFP], human chorionic goandotrophin [HCG] and unconjugated esteriol [E2]. Results were confirmed by doing routine karyogram on cultured amniotic fluid. Groups 2 comprised suspected cases with sex chromosomal disorders including neonates with ambiguous genitalia [64 cases] and adults with primary amenorrhea [69 cases] or infertility [38 cases]. They were subjected to a diagnostic workup including. Among the pregnant women group, seven were found to be at a high risk of having DS fetuses including 3 cases with a history of affected off-springs, 2 cases with age above 35 years, and 2 cases with high triple test. Only one case had positive trisomy 21 on interphase FISH confirmed by karyogram on cultured amniotic cells. The other 6 ladies had normal FISH confirmed by karyograms. Regarding the other group, 5 cases out of the 9 females were proved to be feminized males, one proved mosaic turner, one proved mixed gonadal dysgenesis and 2 normal females. On the other hand one out of three males were proved to be verilized female while the other one was a male with incomplete testicular feminization and the last one was a male with infertility diagnosed as Klinefelter syndrome at the age of 26 years. Interphase FISH is a rapid, accurate and very sensitive method in sex chromosom and autosomal abnormalities. It adds to the diagnostic utility of routine cytogenetics and its use on interphase nuclei overcomes the difficulty of conventional cytogenetics. It could be used in the prenatal diagnosis of DS in addition to ultrasonography, and triple test