Contingent screening for Down syndrome.
Explore the source record for details and available documents.
Down Syndrome↗
Biomedical subjects
Sandra A Farrell
Publications and source records attributed to Sandra A Farrell.
Molecular characterization of an inherited ring (19) demonstrating ring opening.
Ring chromosomes arise following breakage in both chromosome arms and rejoining of the centric segment at the broken ends or by end-to-end fusion of the telomeres. The phenotype of ring carriers is unpredictable, and developmental abnormalities may occur even when the ring appears to be structurally balanced. This is believed to be due to mitotic instability from abnormal segregation and sister chromatid exchange in somatic cells. Although ring chromosomes usually arise as de novo events, transmittal from mosaic carriers to offspring sometimes occurs. In such cases, offspring with ring mosaicism in combination with a normal cell line remain unexplained. In this report, we used detailed molecular and cytogenetic analyses of a prenatally detected, inherited ring (19) to observe the behavior of the ring chromosome in culture, and to investigate the mechanism of inherited ring chromosome mosaicism.
Amniocentesis↗
Fetus with renal agenesis and Smith-Lemli-Opitz syndrome.
Explore the source record for details and available documents.
Abnormalities, Multiple↗
A novel lysozyme mutation Phe57Ile associated with hereditary renal amyloidosis.
BACKGROUND: Variant forms of lysozyme, a ubiquitous bacteriolytic enzyme, are known to lead to hereditary non-neuropathic renal amyloidosis and, so far, three different mutations of the lysozyme gene have been reported. In this study, we report a novel lysozyme variant, Phe57Ile, associated with renal amyloidosis in three patients in one Italian Canadian family. METHODS: The proband was a 52-year-old woman who developed renal failure at the age of 42 years. Renal biopsy demonstrated replacement of glomeruli by amyloid. Her younger sister and her younger daughter who underwent renal transplantation also had renal amyloidosis. The proband's older daughter and her niece were in good health. To elucidate pathogenesis of this hereditary renal amyloidosis, DNA analyses of the lysozyme gene, including single strand confirmation polymorphism, direct DNA sequence, and restriction fragment length polymorphism analyses, were performed. RESULTS: DNA analyses of the lysozyme gene revealed a T to A transversion at the first position of codon 57 of the lysozyme gene in the proband, her sister, and her affected and unaffected daughters, indicating a replacement of Phe by Ile at residue 57. In addition, DNA sequencing demonstrated a C to A transversion at the second position of codon 70, denoting a replacement of Thr by Asn at residue 70, in the proband's sister and her niece. Thus, the proband's sister is compound heterozygous for the Phe57Ile and Thr70Asn alleles. CONCLUSION: Distinctive clinical features in patients of this family are nephropathy due to renal amyloidosis. Our results indicate that the novel lysozyme variant Phe57Ile is associated with renal amyloidosis in this family. From our results, a clear relation between the Thr70Asn polymorphism and renal amyloidosis could not be demonstrated.
Amyloidosis↗
Lack of expression of XIST from a small ring X chromosome containing the XIST locus in a girl with short stature, facial dysmorphism and developmental delay.
A 46,X,r(X) karyotype was found in a three and a half year old girl with short stature, facial dysmorphism and developmental delay. The clinical findings were consistent with the phenotype described in a limited number of patients with small ring X chromosomes lacking the XIST locus, a critical player in the process of X chromosome inactivation. Surprisingly, in our patient, fluorescent in situ hybridisation demonstrated that the XIST locus was present on the ring X. However, expression studies showed that there was no XIST transcript in peripheral blood cells, suggesting that the ring X had not been inactivated. This was confirmed by the demonstration that both of the patient's alleles for the androgen receptor gene were unmethylated, and that both of the patient's ZXDA alleles were expressed. The active nature of the ring X would presumably result in overexpression of genes that may account for the developmental delay observed for the patient. Using polymorphic markers along the X chromosome, the ring X was determined to be of paternal origin with one breakpoint in the long arm between DXS8037 and XIST and one in the short arm in Xp11.2 between DXS1126 and DXS991. To attempt to determine why the XIST gene failed to be expressed, the promoter region was sequenced and found to have a base change at the same location as a variant previously associated with nonrandom X chromosome inactivation. This mutation was not seen in over one hundred normal X chromosomes examined; however, it was observed in the paternal grandmother who did not show substantial skewing of X chromosome inactivation.
Abnormalities, Multiple↗
Double-positive maternal serum screening results for down syndrome and open neural tube defects: An indicator for fetal structural or chromosomal abnormalities and adverse obstetric outcomes.
OBJECTIVE: The study was designed to evaluate whether double positive maternal serum screening results for Down syndrome and open neural tube defects indicate an increased risk of adverse perinatal outcome. STUDY DESIGN: A retrospective case-control study was conducted. In a cohort of 170,394 women who underwent maternal serum triple screening in Ontario, Canada, between October 1995 and September 1998, 189 women received positive screening results for both Down syndrome and neural tube defects. Each case was matched to 5 control subjects who had negative screening results for test center, maternal age, and specimen date. The risks for adverse perinatal outcomes were compared. RESULTS: Women with double-positive screening results had significantly higher risks of having fetuses with structural abnormalities (odds ratio, 14.5) and chromosomal anomalies (odds ratio, 36.3). They also had higher risks of having preeclampsia (odds ratio, 6.7), small-for-gestational age (odds ratio, 9.7), preterm delivery (odds ratio, 5.9), miscarriage, and intrauterine fetal death (odds ratio, 11.8). CONCLUSION: Double-positive maternal serum screening results are associated with fetal structural and chromosomal abnormalities and/or adverse pregnancy outcomes. Close fetal and maternal surveillance are indicated when such pregnancies are identified.
Case-Control Studies↗