Two novel familial balanced translocations t[8;11][p23;q21] and t[6;16][q26;p12] implicated in recurrent spontaneous abortion

Reciprocal translocations represent one of the most common structural rearrangements observed in humans. Estimates of the population frequency range from 1/673 to 1/1000. We have described two novel balanced translocations in two unrelated families who experienced Recurrent Spontaneous Abortions [RSA] following their separate non-consanguineous marriages. Initial cytogenetic studies were performed on cultured blood cells. High resolution GTG-banding analysis using cytovision software performed on their chromosomes revealed a novel balanced translocation t[8;11][p23;q21] in a brother [45 years] and his sister [27 years] in one family. The second novel balanced translocation t[6;16][q26;p12] was observed in a consanguineous couple with 4 RSA. These two families have an increased risk of having children with unbalanced karyotypes or RSA, because of incorrect chromosomal segregation during meiosis

Gene dosage analysis of proximal spinal muscular atrophy carriers using real-time PCR

Autosomal recessive spinal muscular atrophy is a disease resulting from homozygous absence of SMN1 gene in approximately 94% of SMA patients. To identify patients who retained a single SMN1 copy, SMN1 dosage analysis was performed by quantitative Real-time PCR using SYBR green dye. SMN1 dosage analysis results were utilized to identify carriers before offering prenatal diagnosis. Carrier testing was performed for 150 individuals. Copy number of the SMN1 gene was determined by the comparative threshold cycle [Ct] method and human serum albumin gene was used as a reference. Analysis of 150 DNA samples with quantitative PCR determined the number of SMN1 gene copies. Of these, 50 [33.33%] cases had one SMN1 gene copy, 87 [58%] had two copies and 13 [8.66%] did not have any copies of SMN1. The homozygous SMN1 deletion ratio was 0.00 and deletion of one copy of SMN1 gene ratio ranged from 0.3 to 0.58. This report demonstrates modification of risk estimation for the diagnosis and detection of SMA carriers by accurate determination of SMN1 copy number. SMN1 copy number analysis is an important parameter for identification of couples at risk of having children affected with SMA. It also reduces unwarranted prenatal diagnosis for SMA. Furthermore, the dosage analysis might be useful for the counseling of clinically suspected SMA patients with negative diagnostic SMA tests

Evaluation of polymerase chain reaction for diagnosis of "tuberculous pleurisy"

Differential diagnosis between tuberculous pleurisy [TBP] and non-tuberculosis pleural effusion represents a critically important clinical problem. In recent years, several noninvasive methods have been found for diagnosis of tuberculous pleurisy. This study aimed to evaluate the value of detection of the genome of Mycobacterium tuberculosis [MTB] by polymerase chain reaction [PCR] method for the diagnosis of tuberculous pleurisy and compare the results with those of conventional methods. In this cross-sectional study, we studied 62 patients [42 men and 20 women] with pleural effusion in Ghaem Hospital, affiliated to Mashhad University of Medical Sciences from January 2006 to June 2007. A total of 20 patients had tuberculous pleurisy [45.4%], 15 patients had malignant pleural effusion [34%], 3 patients had pleural effusion with various "non-tuberculosis non-malignant" etiologies [6.8%] and 6 patients had transudative pleural effusion [13.6]. The sensitivity, specificity, positive predictive value and negative predictive value of PCR in tuberculous pleurisy were 85%, 100%, 100% and 88.8%, respectively. The value of PCR test and pleural biopsy was similar in the diagnosis of TBP. However, PCR detected MTB in pleural effusion when conventional pleural biopsy failed to do so

Rare gross deletion in T-cell immune regulator-1 gene in Iranian family with infantile malignant osteopetrosis

Infantile malignant osteopetrosis [arOP] is an autosomal recessive disorder. Mutations in the T-cell immune regulator 1 [TCIRG1] gene were found as the cause of arOP. We found the first Iranian patient with a rare gross deletion in this gene. The patient was a 5-year-old girl with macrocephaly, facial dysmorphism, blindness, mental retardation, hepatosplenomegaly, pancytopenia, and osteosclerotic changes in the skull and limb. Molecular analysis was performed using reverse transcriptase-polymerase chain reaction for exons 10-19 of the TCIRG1 gene followed by whole gene sequencing. She showed a 275 bp unexpected amplified segment. Sequencing revealed a gross deletion in exons 10-15 transcript region of TCIRG1 that affected codon 389 to 518. Various types of mutations in the TCIRG1 gene in arOP have been reported, however, gross deletions are reported rarely. This gross deletion is the first mutation reported among Iranian patients in this gene. This deletion is also the largest deletion of TCIRG1 gene reported to date

Nager's acrofacial dysostosis with hypertrophic cardiomyopathy

Nager syndrome is a rare condition associated with craniofacial malformations such as, micrognathia, zygomatic hypoplasia, external ear malformations, and preaxial limb deformities. This report features a case of Nager syndrome occurring in a one-year-old boy showing microretrognathia, thumb hypoplasia, brachydactyly, hexadactyly, and hypertrophic cardiomyopathy, characteristics not usually encountered in published cases