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Biomedical subjects

A Milunsky

Publications and source records attributed to A Milunsky.

At least 19 recordsLinked to original sources
PubMed1992

First prenatal diagnosis of X-linked lymphoproliferative disease.

A family study was performed in order to diagnose X-linked lymphoproliferative (XLP) disease in a fetus. The molecular genetic analysis indicated that the fetus, as well as its healthy 7-year-old brother, inherited XLP. Analysis of immunoglobulin subclasses from the 7-year-old brother supported the DNA-based diagnosis. This is the first XLP family of African descent.

Autoradiography↗
PubMed1992

Maternal heat exposure and neural tube defects.

OBJECTIVE: To determine if exposure to hot tub, sauna, fever, or electric blanket during early pregnancy was associated with an increased risk for neural tube defects (NTDs). DESIGN: Prospective follow-up study. SETTING: Mostly private obstetric practices, primarily in New England. PARTICIPANTS: A cohort of 23,491 women having serum alpha-fetoprotein screening or an amniocentesis were identified. Complete exposure and outcome information was available for 97% of these women. OUTCOME MEASURES: Relative risks (RRs) were used to compare incidence of NTD in those exposed to heat with those who were not exposed to any heat. Crude RRs were calculated directly from the data. Unconfounded RRs were calculated using logistic regression. RESULTS: Women reporting any heat exposure (sauna, hot tub, fever, or electric blanket) in early pregnancy had a crude risk of their fetuses developing NTD of 1.6 (95% CI [confidence interval], 0.9 to 2.9). Women reporting exposure to sauna, hot tub, or fever in early pregnancy had a crude risk of their fetuses developing NTD 2.2 times that of women without heat exposure (95% CI, 1.2 to 4.1). For hot tub use, the crude RR was 2.9 (95% CI, 1.4 to 6.3); for sauna, 2.6 (95% CI, 0.7 to 10.1); for fever, 1.9 (95% CI, 0.8 to 4.1); and for electric blanket, 1.2 (95% CI, 0.5 to 2.6). Multivariate adjusted RRs for individual heat sources, after controlling for maternal age, folic acid supplements, family history of NTD, and exposure to other heat sources, were for hot tub use, 2.8 (95% CI, 1.2 to 6.5); sauna, 1.8 (95% CI, 0.4 to 7.9); fever, 1.8 (95% CI, 0.8 to 4.1); and electric blanket, 1.2 (95% CI, 0.5 to 2.6). When only hot tub, sauna, and fever were considered and the women's exposure to each tallied, compared with no heat exposure, the RR for NTDs increased from 1.9 (95% CI, 0.9 to 3.7) after one type of heat exposure to 6.2 (95% CI, 2.2 to 17.2) after two types of heat exposure. CONCLUSIONS: Exposure to heat in the form of hot tub, sauna, or fever in the first trimester of pregnancy was associated with an increased risk for NTDs. Hot tub exposure appeared to have the strongest effect of any single heat exposure. Exposure to electric blanket was not materially associated with increased risk for NTDs.

Cohort Studies↗
PubMed1992

Cytogenetic studies of an adrenal cortical carcinoma.

Cytogenetic findings in the third reported case of adrenal cortical carcinoma are described. In contrast to the two previous cases, hypodiploidy characterized almost all cells, which had as many as eight abnormal chromosomes in each cell analyzed.

Adrenal Cortex Neoplasms↗
PubMed1992

Congenital bilateral absence of the vas deferens. A primarily genital form of cystic fibrosis.

OBJECTIVE: Almost all males with cystic fibrosis (CF) have absent vasa deferentia. It has been suggested that otherwise healthy males with congenital bilateral absence of the vas deferens (CBAVD), previously considered a distinct genetic entity, have an increased frequency of CF gene mutations. This study examined the genetic commonality of these two disorders. DESIGN: We typed six common CF gene mutations in 25 patients with CBAVD. Additional rare mutations were sought using single-stranded conformation polymorphisms and direct DNA sequencing. When rare mutations were found, they were sought in a large sample of both CF patients and obligate CF carriers to exclude them as polymorphisms. SETTING: All the patients presented to a male infertility clinic of a teaching hospital. SUBJECTS: Twenty-five unselected, unrelated azoospermic men with CBAVD, most of them of Northern European ancestry. RESULTS: Sixteen (64%) of the 25 men with CBAVD had at least one detectable CF mutation, 16 times the expected frequency (P less than .001). Moreover, we have thus far determined that three of these 16 men are compound heterozygotes, one of whom has a mutation not previously described. Analyses continue on patients who have yet to yield a detectable mutation. CONCLUSIONS: Some, if not all, otherwise healthy men with CBAVD reflect a newly recognized, primarily genital, phenotype of CF. Prior to sperm aspiration to remedy infertility, CF mutation analysis should be recommended for them and their partners, as well as for their relatives.

Adult↗
PubMed1992

An exonic mutation in the HuP2 paired domain gene causes Waardenburg's syndrome.

Here we report the identification and characterization of a gene defect causing Waardenburg's syndrome with hearing loss in a large Brazilian family. This demonstrates a mutation causing Waardenburg's syndrome as well as a mutation causing a form of congenital deafness. The mutation was found in the HuP2 gene, a member of the paired domain family of proteins that bind DNA and regulate gene expression. The mutation occurred in 100% of the cases with the disease in this family and was absent in a random sample of 50 unrelated control subjects. Identification of the Waardenburg's syndrome gene and future characterization of its gene product is likely to increase our understanding of the pathogenesis of this disorder and may allow prevention of deafness of this type.

Amino Acid Sequence↗
PubMed1992

Maternal zinc and fetal neural tube defects.

Among the factors implicated in the heterogeneous etiology of neural tube defects (NTDs) is the trace element zinc (Zn). In a case-control study, we collected midtrimester maternal toenail samples for multiple trace element analyses, including Zn, which were assayed by neutron activation analysis. We studied 17 women with NTD offspring and 1,787 controls. The crude OR for NTD comparing Zn values greater than normal range to normal Zn values was 3.2 (95% CI 1.1,9.7). These results were not materially affected when adjustment was made for folic acid supplementation. An overall increased risk for NTD associated with increasing toenail Zn was also evident. A matched subset of 17 cases and 73 controls yielded a crude OR of 3.1 (95% CI 0.9,10.3) when cases with elevated Zn (greater than or equal to 120 ppm) were compared to those with normal Zn. Matched analyses controlling for folic acid supplements, family history of NTD, assay batch, age of mother and year of delivery yielded an OR of 5.0 (95% CI 1.1,21.6). This study reveals an association between increased toenail Zn in the second trimester of pregnancy and the risk of having a child with an NTD. Whether Zn sequestration has resulted in relative Zn deficiency at the site of neural tube closure remains uncertain.

Case-Control Studies↗
PubMed1992

Cytogenetic studies of eight squamous cell carcinomas of the head and neck. Deletion of 7q, a possible primary chromosomal event.

Cytogenetic analysis was performed on the metaphase spreads obtained from primary cultures of eight squamous cell carcinomas (SCCa) of the head and neck. Despite a variety of tumor sites and clinical stages, four of eight tumors studied showed the same interstitial deletion of a portion of the q arm of chromosome 7, i.e., del(7)(q22q34). In one tumor, this was the sole chromosome abnormality present. Three tumors showed multiple chromosome rearrangements, including deletion at 7q. Three tumors showed multiple rearrangements but did not have del(7q). One tumor had an apparently, normal karyotype. The implications for del(7q) as a primary chromosomal event in SCCa are discussed.

Aged↗
PubMed1992

Abnormalities of chromosome 22 in meningiomas and confirmation of the origin of a dicentric 22 by in situ hybridization.

We report three cases of meningioma. Case 1 had a dicentric chromosome number 22 resulting in partial monosomy for a portion of the q-arm, i.e., 46,XX,idic(22)(pter-->q11.2::q11.2-->pter) and 46,XX,psu dic(22)(pter-->q11.2::q11.2-->pter), which was the sole clonal abnormality. The origin of the dicentric chromosome from 22 was confirmed by in situ hybridization studies, using biotin-labeled alpha centromeric DNA probes for the acrocentric chromosomes. Case 2 had two distinct clonal abnormalities: deletion of 22q and monosomy of 22. Case 3 also had a deleted 22q.

Aged↗
PubMed1992

A new transthyretin mutation associated with amyloidotic vitreous opacities. Asparagine for isoleucine at position 84.

An inherited type of amyloidosis was suspected in an individual of Italian descent who presented with vitreous opacities. Although no family history of amyloidosis was apparent, the patient's transthyretin gene was examined and found not to possess any of the known transthyretin mutations. Complete DNA sequencing revealed a substitution of adenine for thymine in the second base of codon 84 causing an amino acid change of asparagine for isoleucine. The mutation was confirmed by demonstrating the loss of an Sfa N1 restriction endonuclease site. Allele-specific DNA amplification by polymerase chain reaction also was used to confirm the mutation. Either of these tests can be used for diagnosis. Asparagine 84 represents the second mutation associated with amyloidosis to occur at codon 84.

Aged↗
PubMed1992

Deletion of 15q12 in Angelman syndrome: report of 3 new cases.

Deletion of 15q12 has been reported in patients with Angelman syndrome (AS). We report chromosome studies showing del(15q12) in three new cases, diagnosed as having AS. We were also able to determine, through heteromorphism studies, that the origin of the deleted chromosome in all three probands is maternal. This is a consistent finding in previously reported cases of AS.

Adult↗
PubMed1992

Familial amyloidotic polyneuropathy: a new transthyretin position 30 mutation (alanine for valine) in a family of German descent.

Familial amyloidotic polyneuropathy (FAP) is a dominantly inherited form of amyloidosis usually associated with an abnormal transthyretin (TTR), previously known as prealbumin. Several disease-related variants of the protein, each with a different amino acid substitution and correlating DNA point mutation, have been identified. The TTR gene from a patient suffering from this disorder was asymmetrically amplified and directly sequenced, revealing a cytosine for thymine substitution in the second base of codon 30 and the creation of a novel Cfo I restriction endonuclease site in exon 2. This mutation results in a previously undescribed substitution of an alanine for valine in the final TTR protein. Analysis of the amino acid mutation reveals it to be a hydrophilic substitution at a hydrophobic core position. Alanine at position 30 represents the second FAP-associated mutation at position 30 in TTR.

Adult↗
PubMed1991

Partial duplication of Xp: a case report and review of previously reported cases.

We report clinical and cytogenetic findings on a 24-year-old woman with short stature, irregular menses, and other anomalies suggestive of Ullrich-Turner syndrome (UTS). Chromosome analysis documented a de novo duplication of Xp21 without any apparent microscopic deletion. DNA studies showed that part of band Xp22.1 is also duplicated. The clinical findings are compared with 5 other patients with dup(Xp).

Adult↗
PubMed1991

Maternal serum human chorionic gonadotropin levels in twin pregnancies.

Introduction of combined screening with maternal serum alpha-fetoprotein and human chorionic gonadotropin (MShCG) assays for fetal chromosome defects requires establishment of the normal range for twins. This report documents that the normal range for MShCG between 15 and 19 weeks in twin gestations was 1.84-2.41 multiples of the singleton median. Of the 192 twin pregnancies studied, 31.7 and 47.9 per cent had MShCG values greater than or equal to 2.5 and greater than or equal to 2.0 multiples of the singleton median, respectively.

Chorionic Gonadotropin↗
PubMed1991

Alpha-fetoprotein and acetylcholinesterase are not predictive of fetal junctional epidermolysis bullosa, Herlitz variant.

Junctional epidermolysis bullosa, Herlitz variant (junctional EB-Herlitz) is a lethal autosomal recessive skin disorder currently amenable to prenatal diagnosis only by direct analysis of fetal skin. However, elevated levels of alpha-fetoprotein, as well as the presence of acetylcholinesterase in amniotic fluid, have been associated with other severe fetal genodermatoses. Fetal skin samplings were performed in ten pregnancies at risk for fetal junctional EB-Herlitz, with three fetuses affected on the basis of electron microscopic detection of blisters within the lamina lucida and abnormal hemidesmosomes. In neither affected nor unaffected pregnancies were maternal serum or amniotic fluid alpha-fetoprotein levels elevated. Moreover, alpha-fetoprotein levels in both maternal serum and amniotic fluid were not statistically different comparing affected and unaffected fetuses. Acetylcholinesterase was not present in the amniotic fluid samples of the three affected pregnancies. Unlike other severe fetal genodermatoses, neither alpha-fetoprotein nor acetylcholinesterase was predictive of junctional EB-Herlitz.

Acetylcholinesterase↗