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Small supernumerary marker chromosomes (sSMCs), or markers, are abnormal chromosomal fragments that can be hereditary or de novo. Despite the importance of sSMCs diagnosis, de novo sSMCs are rarely detected during the prenatal diagnosis process. Usually, prenatally diagnosed de novo sSMCs cannot be correlated with a particular phenotype without knowing their chromosomal origin and content; therefore, molecular cytogenetic techniques are applied to achieve this goal. The present study aimed to characterize an sSMC in a case of Klinefelter syndrome using an in-house microsatellite analysis method and fluorescent in situ hybridization (FISH) technique. Amniotic fluid was collected from a pregnant woman who was considered to have risk factors for trisomy higher than the screening cut-off. Karyotype analysis was followed by the amplification of different microsatellite loci and FISH technique. Karyotype analysis identified a fetus with an extra X chromosome and also an sSMC with unknown identity. Further investigation of the parents showed that the sSMC is de novo. Microsatellite amplification by quantitative fluorescent PCR (QF-PCR) and FISH analysis showed that the sSMC is a derivative of chromosome 18. Eventually, the patient decided to terminate the pregnancy. Here, the first case of the coincidence of sSMC 18 in a Klinefelter fetus is reported. [ABSTRACT FROM AUTHOR]

Background: Progressive familial intrahepatic cholestasis (PFIC) is a heterogeneous group of hepatic disorders that can progress rapidly, leading to cirrhosis and death due to liver failure. Mutations and variations in three genes, including ATP8B1, ABCB11, and ABCB4, have been reported to be the main genetic cause of three subtypes of this disorder including PFIC1, PFIC2, and PFIC3, respectively. Objectives: Therefore, the aim of this study was to investigate more common mutations and variations associated with PFIC considering clinical and Para-clinical features of the disease. Methods: Thirty-five unrelated patients with PFIC from the south of Iran were selected randomly among all PFIC patients referring to Namazi hospital, affiliated to Shiraz University of Medical Sciences. Genomic DNA was extracted from the peripheral blood lymphocytes. Sequences related to these variations were then amplified by PCR in the 35 cholestasis patients and analyzed by Sanger® sequencing. Results: The results showed that there was no variation in interest exon of ABCB4. Moreover, in ATP8B1, there was no prevalent mutation and only an unknown significant variation (c.*11 01+366G> A) was found. However, in the ABCB11 gene, different variations were found including c.1434 + 174G > A, c.1434 + 70C > T, c.1331T > C (p.Val444Ala, a common variant proposed to be associated with cholestasis), c.1309-93G > A, c.1309-165C > T. Also, 11 and 13 cases showed heterozygote and homozygote, respectively, for V444A variation of the ABCB11 gene. Conclusions: The allele frequency of V444A in this study was 52.8%. This variation has been previously implicated with higher frequencies in ICP and DIC than normal subjects, suggesting that this variation may become disease-relevant in certain conditions. [ABSTRACT FROM AUTHOR]