Thyroxin-binding globulin deficiency in a boy with fragile X syndrome: a case report

Fragile X syndrome [FXS] is the most common known genetic cause of male intellectual disability. A wide variety of medical problems has been reported in FXS syndrome including seizures, facial abnormalities, macroorchidism, and autistic disorders. Here we reported a 9-year-old boy with fragile X syndrome that was confirmed through karyotyping and mental retardation. Initially, he was diagnosed as hypothyroidism when he was 15 months old. However, due to unusual clinical presentation, we re-evaluated the patient according to his history and clinical findings. Subsequently, targeted laboratory tests were performed and the results were indicative for thyroxin-binding globulin [TBG] deficiency in our patient. Therefore, levothyroxine was discontinued and one month later, laboratory tests were repeated and his diagnosis confirmed. As inherited TBG deficiency might also be X-linked, FXS and TBG deficiency may be coincidental findings in the patient

Chromosomal analysis of couples with repeated spontaneous abortions in northeastern Iran

Cytogenetic study of reproductive wastage is an important aspect in deter-mining the genetic background of early embryogenesis. Approximately 15 to 20% of all pregnancies in humans are terminated as recurrent spontaneous abortions [RSAs]. The aim of this study was to detect chromosome abnormalities in couples with RSAs and to compare our results with those reported previously. In this retrospective study, the pattern of chromosomal aberrations was evaluated during a six-year period from 2005 to 2011. The population under study was 728 couples who attended genetic counseling services for their RSAs at Pardis Clinical and Genetics Laboratory, Mashhad, Iran. In this study, about 11.7% of couples were carriers of chromosomal aberrations. The majority of abnormalities were found in couples with history of abortion, without stillbirth or livebirth. Balanced reciprocal translocations, Robertsonian translocations, inversions and sex chromosome aneuploidy were seen in these cases. Balanced reciprocal translocations were the most frequent chromosomal anomalies [62.7%] detected in current study. These findings suggest that chromosomal abnormalities can be one of the important causes of RSAs. In addition, cytogenetic study of families who experienced RSAs may prevent unnecessary treatment if RSA are caused by chromosomal abnormalities. The results of cytogenetic studies of RSA cases will provide a standard protocol for the genetic counselors in order to follow up and to help these families

Pattern of chromosomal aberrations in patients from North East Iran

Chromosomal aberrations are common causes of multiple anomaly syndromes. Recurrent chromosomal aberrations have been identified by conventional cytogenetic methods used widely as one of the most important clinical diagnostic techniques. In this retrospective study, the incidences of chromosomal aberrations were evaluated in a six year period from 2005 to 2011 in Pardis Clinical and Genetics Laboratory on patients referred to from Mashhad and other cities in Khorasan province. Karyotyping was performed on 3728 patients suspected of having chromosomal abnormalities. The frequencies of the different types of chromosomal abnormalities were determined, and the relative frequencies were calculated in each group. Among these patients, 83.3% had normal karyotypes with no aberrations. The overall incidences of chromosomal abnormalities were 16.7% including sex and autosomal chromosomal anomalies. Of those, 75.1% showed autosomal chromosomal aberrations. Down syndrome [DS] was the most prevalent autosomal aberration in the patients [77.1%]. Pericentric inversion of chromosome 9 was seen in 5% of patients. This inversion was prevalent in patients with recurrent spontaneous abortion [RSA]. Sex chromosomal aberrations were observed in 24.9% of abnormal patients of which 61% had Turner's syndrome and 33.5% had Klinefelter's syndrome. According to the current study, the pattern of chromosomal aberrations in North East of Iran demonstrates the importance of cytogenetic evaluation in patients who show clinical abnormalities. These findings provide a reason for preparing a local cytogenetic data bank to enhance genetic counseling of families who require this service

Identification of Xq22.1-23 as a region linked with hereditary recurrent spontaneous abortion in a family

Recurrent spontaneous abortion [RSA] is one of the most common health complications with a strong genetic component. Several genetic disorders were identified as etiological factors of hereditary X linked RSA. However, more genetic factors remain to be identified. In this study we performed linkage analysis on a large X linked RSA pedigree to find a novel susceptibility locus for RSA. A linkage scan using 11 microsatellites was performed in 27 members of a large pedigree of hereditary X-linked RSA. Two point parametric Linkage was performed using Superlink v 1.6 program. Evidence of linkage was observed to markers at Xq23, DXS7133 and at Xq22.1 DXS101, with LOD score of 3.12 and 1.60, respectively. Identified locus in this study may carry a responsible gene in RSA. Narrowing down of this region may leads to identification of this gene

Novel mutation in the SLC19A2 gene in thiamine-responsive megaloblastic anemia [Rogers' syndrome]

The Thiamine Transporter gene SLC19A2 is the only gene known to be associated with TRMA. This syndrome is a trial clinical characterized by megaloblastic anemia, nonautoimmune diabetes mellitus and sensory-neural hearing loss. Described here are three children from consanguineous Iranian families with thiamine - responsive megaloblastic anemia [TRMA] or Rogers' syndrome. Case one and two were siblings of healthy first-cousin parents and case three from a healthy second-cousin couple. These cases presented with hyperglycemia, anemia, and hearing loss. Thiamine reversed the anemia and there was a satisfactory response for the hyperglycemia as well. In all three patients, direct sequencing revealed a homozygous mutation c.38 G>A [P.E.128K] resulting in the substitution of glutamic acid to lysine at position 128 in exon 2 of the SLC19A2 gene on chromosome 1q23.3. This novel mutation was confirmed by the PCR RFLP assay of more than 100 control alleles. TRMA or Rogers' syndrome should be considered for patients with diabetes [DM] and other symptoms, including hearing loss and anemia. Early diagnosis can assist families in planning future pregnancies. The administration of thiamine ameliorates the megaloblastic anemic condition and produces a better response in DM

Clinical and molecular genetic analysis of Iranian patients with neonatal diabetes demonstrating mutations in KCNJ11 gene

We screened the KCNJ11 gene from 35 individuals clinically diagnosed with type 1 diabetes mellitus under the age of 6 months in 3 years duration. Six different heterozygous missense mutations were found in 7 of the 35 probands, which accounted for 20% of all individuals. A novel mutation W68R [No Locus, GU170814; 2009] was identified in the kir6.2, the pore-forming subunit of the KATP channels from pancreatic beta -cells. Our results demonstrated that activating mutations in KCNJ11 gene could cause Permanent Neonatal Diabetes Mellitus [PNDM] with onset prior to six months

P21 [Waf1/Cip1] gene polymorphisms and possible interaction with cigarette smoking in esophageal squamous cell carcinoma in northeastern iran: a preliminary study

The incidence of esophageal squamous cell carcinoma [ESCC] is very high in northeastern Iran. However, the genetic predisposing factors to ESCC in this region have not been clearly defined. The P21 [waf1/cip1] gene is involved in the arrest of cellular growth, as induced by the p53 tumor suppressor gene. Two polymorphisms of p21 gene in codon 31 [p21 C98A, dbSNP rs1801270] and the 3'UTR [p21 C70T, dbSNP rs1059234] ma-y affect protein expression and play a role in cancer susceptibility. The present study aimed to investigate the association of p21 polymorphisms in codon 31 and the 3'UTR, and cigarette smoking on the risk of ESCC in northeastern Iran. A case-control study was carried out to detect the p21 polymorphism in the 3'UTR and codon 31 of samples from 126 ESCC cases and 100 controls from 2006 to 2007. There were no significant differences of age and sex between cases and controls. Genotyping of p21 polymorphisms were determined with the PCR-RFLP method. Conditional logistic regression was used to adjust for potential confounders. None of the p21 genotypes were significantly associated with risk of ESCC, even after adjusting for age and gender [P=0.52, OR=1.24; 95%CI: 0.63-2.42]. However, the presence of these polymorphisms in combination with cigarette smoking had a synergistic interaction in ESCC carcinogenesis in northeastern Iran [P=0.02, OR=8.38; 95%CI: 1.03-67.93]. Our data suggests that these two p21 polymorphisms, both alone and in combination, are not genetic susceptibility biomarkers for ESCC. However, their interaction with cigarette smoking may influence the susceptibility to ESCC development in northeastern Iran

Rapid DNA extraction protocol from stool, suitable for molecular genetic diagnosis of colon cancer

Colorectal cancer [CRC] is one of the most common forms of cancers in the world and is curable if diagnosed at the early stage. Analysis of DNA extracted from stool specimens is a recent advantage to cancer diagnostics. Many protocols have been recommended for DNA extraction from stool, and almost all of them are difficult and time consuming, dealing with high amount of toxic materials like phenol. Their results vary due to sample collection method and further purification treatment. In this study, an easy and rapid method was optimized for isolating the human DNA with reduced PCR inhibitors present in stool. Fecal samples were collected from 10 colonoscopy-negative adult volunteers and 10 patients with CRC. Stool [1 g] was extracted using phenol/chloroform based protocol. The amplification of P53 exon 9 was examined to evaluate the extraction efficiency for human genomic targets and also compared its efficiency with Machiels et al. and Ito et al. protocols. The amplification of exon 9 of P53 from isolated fecal DNA was possible in most cases in 35 rounds of PCR using no additional purification procedure for elimination of the remaining inhibitors. A useful, rapid and easy protocol for routine extraction of DNA from stool was introduced and compared with two previous protocols