فهرست مطالب nayereh nouri

Consanguineous marriage, which is common in many regions in the world, has absorbed much attention as a causative factor in raising the incidence of genetic diseases. The adverse effects may be attributed to the expression of the genes received from common ancestors and mortality and morbidity of the offspring. Iran has a high rate of consanguineous marriages. In recent years genetic counseling has come to be considered in health care services. This cross-sectional study was conducted in order to determine the prevalence and types of consanguineous marriages in the genetic clinics in Isfahan. We aimed to define the different types of marriages, specific categories of genetic disorders associated with consanguineous marriages, and mode of inheritance in the family tree. We also narratively reviewed the ethical aspects of the issue. The data were collected using a simple questionnaire. A total number of 1535 couples from urban and rural areas formed the study population. The marriages were classified according to the degree of the relationship between couples, including: double cousin, first cousin, first cousin once removed, second cousin and beyond second cousin. The SPSS software version 16 was used for data analysis.Data obtained through genetic counseling offered during a 5-year period revealed that 74.3% had consanguineous relationships, 62.3% were first cousins, 1% were double cousins and 7.8% were second cousins. In addition, 76% of the couples had at least one genetic disease in their family tree. Related ethical issues were also considered in this study, including autonomy and informed decision making, benefit and harm assessment, confidentiality, ethics in research, justice in access to counseling services, financial problems ethics, and the intellectual property of scientific success.

22q11.2 microdeletion syndrome is the most common multiple genetic disorder associated with learning disabilities, developmental delays, immune deficiency, hypocalcemia, and cleft palate. Finding some valid criteria for screening of 22q11.2 deletion syndromes in infants would be very helpful in early diagnosis and treatment.

Since 69% of individuals with 22q11.2 deletion have a palatal abnormality, we studied the prevalence of 22q11.2 deletion syndrome in 378 Iranian patients during a 5-year period, including 291 patients affected with cleft palate only without cleft lip (CPO) and 87 patients affected with velopharyngeal incompetence (VPI) and/or submucous cleft palate (SMCP). DNA copy number was analyzed with multiplex ligation-dependent probe amplification (MLPA) technique.

In our study, 15/378 (3.97%) patients with palatal anomalies showed 22q11.2 deletion. Interestingly, this prevalence between syndromic patients was 15/104 (14.42%).

It seems that SMCP or VPI, in addition to one or more another features of 22q11.2 deletions, especially developmental delay, may be good criteria for molecular investigation of 22q11.2 region.

The Duchenne muscular dystrophy (DMD) gene is located in the short arm of the X chromosome (Xp21). It spans 2.4 Mb of the human genomic DNA and is composed of 79 exons. Mutations in the Dystrophin gene result in DMD and Becker muscular dystrophy. In this study, the efficiency of multiplex ligation-dependent probe amplification (MLPA) over multiplex polymerase chain reaction (PCR) assays in an Iranian population was investigated.

Multiplex PCR assays and MLPA analysis were carried out in 74 patients affected with DMD.

Multiplex PCR detected deletions in 51% of the patients with DMD. MLPA analysis could determine all the deletions detected by the multiplex PCR. Additionally, MLPA was able to identify one more deletion and duplication in patients without detectable mutations by multiplex PCR. Moreover, MLPA precisely determined the exact size of the deletions.

Although MLPA analysis is more sensitive for detection of deletions and duplications in the dystrophin gene, multiplex PCR might be used for the initial analysis of the boys affected with DMD in the Iranian population as it was able to detect 95% of the rearrangements in patients with DMD.

Proximal spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disease characterized by symmetrical proximal muscle weakness and atrophy. According to the severity of the disease and the age of onset, SMA can be divided into three groups. The survival motor neuron (SMN) gene that is located on 5q13 is identified as the disease determining gene. Another gene in this region is neuronal apoptosis inhibitory protein (NAIP), and its functional role in the pathogenesis of SMA has not been fully elucidated. Here, we investigated the correlation between deletions in SMN and NAIP genes with clinical features of SMA patients.

In the current study, 71 unrelated Iranian patients were investigated for the detection of deletions in SMN1 and NAIP genes. Polymerase chain reaction (PCR) was used to detect the deletions of exon 4 and 5 of the NAIP gene. Deletions in exon 7 and 8 of SMN1 gene were detected by RFLP-PCR with DraI and DdeI, respectively.

Our results showed that 51 patients have homozygous deletions in SMN1 and/or NAIP genes. Among these 51 patients, deletion in NAIP gene were found in 35 patients (65.7% of type I, 22.5% type II and 11.42% type III).

Defect in SMN1 gene plays a major role in manifesting of the disease and NAIP (4 and 5) gene acts as a modifying factor in severity of symptoms. Correlation between NAIP gene defect and severity of the disease is confirmed. However, the exact role of NAIP gene in SMA has yet to be fully clarified.

There are contrary results about the role of CACNA1A gene in the causation of common migraine in different populations. However, migraine may be genetically heterogeneous and more studies in different families and populations are required for a definite conclusion. The aim of this study was to surveyed leukocyte genomic DNA mutation of CACNA1A in Iranian migraine patients with [MA] and without aura [MO] who has family history of migraine and we performed a narrative review of all studies that evaluated CACNA1A gene, non-hemiplegic migraine [MA and MO] and FHM [familial hemiplegic migraine]. The 30 patients with family history of migraine were selected for mutations analysis for CACNA1A gene by PCR method. For review, we searched MEDLINE-PUBMED, ISI, Scopus and Cochrane databases up to December 2012. Mutation analysis of the 4 exons of the CACNA1A gene in these patients revealed no mutations in this gene. Direct sequencing revealed a polymorphism previously reported G to A transition in the exon 16 [nt2369, G→A] in 9 patients. In review, the correlation of FHM loci [CACNA1A gene] with MA and MO has been showed in different population and only small population from Caucasians presented this correlation. CACNA1A is most likely not a major susceptibility gene for common migraine in Iranian maigrainous. It’s essential to study more on larger series and covering all 47 exons of the CACNA1A gene to confirm this hypothesis.

Our proband is a 29-year-old man, who is affected with soft cleft palate and hypernasality. A study of about six generations of this family pedigree shows that cleft palate has repeatedly occurred in males, with probably a X-linked recessive pattern of inheritance. Interestingly, the sister of the proband is affected with hypernasality and she has an affected son. This is the first report of X-linked inheritance pattern of cleft palate in Iran.

Ataxia with oculomotor apraxia type 1 (AOA1) shows early onset with autosomal recessive inheritance and is caused by a mutation in the aprataxin (APTX) gene encoding for the APTX protein.

In this study، a 7-year-old girl born of a first-cousin consanguineous marriage was described with early-onset progressive ataxia and AOA، with increased cholesterol concentration and decreased albumin concentration in serum. PCR and direct DNA sequencing was performed after DNA extraction.

Sequencing analysis revealed a novel homozygous deletion in c. 643 and A>T single nucleotide polymorphism in c. 641 in exon 6 of the APTX gene [ENST00000379825].

It seems that this region of exon 6 is probably a hot spot; however، no deletions have been reported in exon 6 yet.

•Velo-cardio-facial syndrome (VCFS) is caused by a submicroscopic deletion on the long arm of chromosome 22 and affects approximately 1 in 4000 persons, making it the second most prevalent genetic syndrome after Down syndrome and the most common genetic syndrome associated with cleft palate. Most of the 22q11.2 deletion cases are new occurrences or sporadic; however, in about 10 % of families, the deletion is inherited and other family members are affected or at risk for passing this deletion to their children. This report describes a 1.5 years-old male child with clinical signs of velo-cardio-facial syndrome (VCFS) presented with heart defect, soft cleft palate, developmental delay, acrocephaly, seizure, MRI abnormalities and descriptive facial feature, such as hypertelorism. Array-CGH test was done to confirm the diagnosis; the result revealed a 2.6 Mbp deletion in 22q11.2 chromosome that containing TBX1 and COMT genes. Our data suggest that haploinsufficiency of TBX1 gene is probably a major contributor to some of the syndrome characteristic signs, such as heart defect. Because of developmental delay and dysmorphic facial feature were observed in the index's mother and relatives, inherited autosomal dominant form of VCF is probable, and MLPA (multiplex ligation-dependent probe amplification) test should be performed for parents to estimate the recurrent risk in next pregnancy.

• In this article, we report a non consanguineous normal couple that had a history of one abortion and a death of 3 years old daughter.•Case report: After genetic counseling and drawing the familial pedigree, we found that man's mother had history of 3 abortions and 2 death of newborns in her non consanguineous marriage. The man has two normal brothers with completely different morphology, body mass index, and facial features from the proband. Chromosomal study with GC-Banding method on proband's whole blood samples show a pericentric inversion of chromosome 9, [Inv (9) (p11-q13)], in the man but the woman had normal karyotype. Then chromosomal analysis was performed for man's mother and she was carrier of this rearrangement such as her son too. Because of non cooperation of other family members, the chromosomal study on other members of family was not possible. • Pericentric inversion of chromosome 9 [Inv (9) (p11-q13)] is one of the frequent chromosomal rearrangements which is consider to be a normal variant with prevalence of 1-3% in population. Although it seems not to correlate with abnormal phenotypes, there have been many controversial reports indicating that it may lead to abnormal clinical conditions such as infertility, congenital heart disease, still birth and dysmorphic features in carriers due to important genes exist in this region that have key rols in gametogenesis, organogenesis and metabolism. In addition, pericentric inversions cause derangement in mating pf homologue chromosomes in meiosis lead to production of abnormal gametes.