[Marfan syndrome and pregnancy. Apropos of 4 cases]. / Syndrome de Marfan et grossesse. A propos de quatre cas.

OBJECTIVES: To create a follow-up protocol for pregnant patients with Marfan syndrome. PATIENTS AND METHODS: We retrospectively reviewed the charts of patients who delivered in the Jeanne de Flandre University Hospital between June 1996 and June 1999. Four pregnant patients with Marfan syndrome were identified. RESULTS: Three of these patients had Bentall procedure. One of them had vaginal delivery and the two others underwent cesarean section. One of these two patients developed aortic valve thrombus at 14 weeks of amenorrhea. The fourth patient did not have surgery and had two vaginal deliveries. DISCUSSION: According to our results and after reviewing literature pregnant patients with Marfan syndrome were divided into two groups. The 1st group was comprised of patients who underwent Bentall procedure. The 2nd one was comprised of patients who did not undergo any surgical procedure. The possibility of vaginal delivery for patients who underwent Bentall procedure (one case) and the interest of Propanolol and anticoagulant treatment are emphasized. CONCLUSION: The multivariant approach of pregnant patients with Marfan syndrome is stressed out with special reference to the potential complications of this syndrome such as aortic dissection and to the problems related to the anticoagulant treatment.

The human fatty acid transport protein-1 (SLC27A1; FATP-1) cDNA and gene: organization, chromosomal localization, and expression.

Uptake of fatty acids into cells is a controlled process in part regulated by fatty acid transport proteins (FATPs), which facilitate the transport of fatty acids across the cell membrane. In this study the structure of the human FATP-1 (HGMW-approved symbol SLC27A1) cDNA and gene was determined, and the expression of its mRNA in human was characterized. Muscle and adipose tissue have the highest levels of FATP-1 mRNA, small intestine has intermediate levels, and FATP-1 mRNA is barely detectable in liver. The human FATP-1 gene has 12 exons and extends over more than 13 kb of genomic DNA. The FATP gene maps to chromosome 19p13.1 by fluorescence in situ hybridization, a region previously suggested to be implicated in the determination of small dense low-density lipoprotein (LDL). Knowledge of the gene structure and chromosomal localization will allow screening for FATP mutations in humans with metabolic disorders, whereas knowledge of its expression pattern and factors regulating its expression could be of importance in understanding its biology.

[Trisomy 18: ultrasound aspects. Report of 40 cases]. / Trisomie 18: aspects échographiques. A propos de 40 observations.

OBJECTIVE: We describe the different ultrasound findings suggestive of trisomy 18. PATIENTS AND METHODS: We conducted a retrospective study in 40 cases of trisomy 18 diagnosed in the department of obstetrics at the Lille University Hospital between 1988 and 1998. RESULTS: Eighty percent of the women in this series were multiparous. Mean maternal age at discovery of the trisomy as 33.2 years and the mean gestational age was 20.4 weeks. Fifty-five percent of the cases were discovered during the second trimester of pregnancy, 22.5% during the third trimester and 22.5% during the first trimester. One ultrasound abnormality, at least, was detected in 36/40 cases (90%) a percentage that reached 96.8% taking into consideration the ultrasound examinations performed during the second and third trimesters (30/31 cases). The most frequently detected ultrasound abnormalities were: intra uterine growth retardation (IUGR: 50%), poly-hydramnios (42.5%), limb abnormalities (42.5%), cardiac defects (30%), facial abnormalities (37.5%), meningomyelocele (32.5%), digestive abnormalities (32.5%), urinary tract abnormalities (27.5%), lymphangiectasia and cystic hygroma (15%), and single umbilical artery (12.5%). Medical termination of pregnancy (TOP) was performed in 28 cases. There was one spontaneous miscarriage at 8 weeks and one in utero death (IUD) at 39 weeks in a patient who desired to continue her pregnancy. In 6 cases, the issue of the pregnancy was unknown because the patients were lost to follow-up. In 4 cases (10%), pregnancy was continued to delivery of live babies that only survived a few minutes to 7 days. CONCLUSION: The ultrasound signs suggestive of trisomy 18 change according to the term of pregnancy. At the first trimester, most of the signs are nonspecific, such as cystic hydroma or lymphangiectasia, and do not suggest the need for a karyotype. At the end of the second trimester, an association of various signs that alone would not be highly suspect suggest the need for further exploration in search of other signs: early IUGR, associated or not with poly-hydramnios, limb abnormalities, cardiac defects, omphalocele, diaphragmatic hernia, meningomyelocele, enlarged cisterna magna, choroid plexus cysts, single umbilical artery, facial dysmorphism, facial cleft, hydronephrosis.

[Prenatal diagnosis of partial trisomy 9p]. / Diagnostic anténatal d'une trisomie 9p partielle.

The prenatal diagnosis of trisomy for the distal half of the short arm of n(o) 9 chromosome (partial trisomy 9p) has been realized from a morphologic ultrasound. A genetic investigation has permitted to establish that this trisomy was due to a bad segregation of a stable translocation present in the patient's mother. To our knowledge, the ultrasound prenatal diagnosis of partial trisomy 9p has never been reported in the literature. The prognosis of this syndrome remains very pejorative and the termination of pregnancy is the most often proposed solution.

Linear and whorled nevoid hypermelanosis versus incontinentia pigmenti: is pigmentary incontinence really a distinctive feature?

This report describes a 3-year-old boy who presented with skin lesions characterized by multiple streaks of hyperpigmentation following Blaschko's lines since 6 weeks of age. The clinical features are consistent with the diagnosis of linear and whorled nevoid hypermelanosis (LWNH), but differ substantially from this entity by the pigmentary incontinence observed on both the paraffin and electron microscopy sections. Despite the presence of pigmentary incontinence, the diagnosis of incontinentia pigmenti (IP) can be ruled out on the basis that the patient is a male, with none of the characteristic anomalies present in this syndrome, and that he never presented with inflammatory or eruptive skin lesions. This observation suggests that pigmentary incontinence may not differentiate IP from LWNH as conclusively as previously reported in the literature.

Gene mapping in Alport families with different basement membrane antigenic phenotypes.

The present study was undertaken to determine whether differences among Alport kindreds in the antigenic phenotypes of their basement membranes result from defects at distinct genetic loci or from allelic mutations at a single locus. We analyzed linkage of the Alport gene to polymorphic loci on the X chromosome in three families with Alport syndrome. In two of the families, epidermal basement membranes of affected members showed altered immunohistologic reactivity with a discriminating antibody (FNS1) that identified a 26 kD peptide in the NCl domain of basement membrane collagen. In the third family epidermal basement membranes of affected individuals reacted normally with the antibody. The disease gene mapped to the Xq21-q22 region of the long arm of the X chromosome in the two families with altered basement membrane antigenicity and in the family with normal basement membrane antigens. We conclude that Alport syndrome in each of these kindreds arose from allelic mutations at a single genetic locus, although we cannot at this time exclude the possibility that two or more tightly linked genes are involved. As the genes for the known chains of type IV collagen are on chromosome 13, our findings suggest that the Alport gene may encode a new basement membrane collagen chain.

Identification of carriers of Duchenne muscular dystrophy: value of molecular analysis.

Currently, molecular methods are the most accurate diagnostic tools for carrier detection and prenatal diagnosis of Duchenne muscular dystrophy (DMD). This report illustrates the value of molecular diagnosis as opposed to previous diagnostic methods, the need for frequent re-evaluations as new methodologies develop, and the necessity for in-depth genetic counseling. In Family 1, the proposita was predicted to be a carrier by an indirect assay (abnormal in vitro muscle ribosomal protein synthesis). DNA analysis using restriction fragment length polymorphisms (RFLPs) indicated that she was not a carrier. She gave birth to a predicted non-affected male, who inherited the gene in question. In Family 2 the proposita, an obligate carrier, was initially evaluated by RFLP analysis. Two pregnancies were monitored by first trimester chorionic villous sampling. Re-evaluation indicated that all affected individuals, including one of the embryos, carried a deletion of the dystrophin gene. The identification of an RFLP within the region containing the deletion allowed unambiguous determination of the carrier status of all individuals.

Absence of detectable chromosomal and molecular abnormalities in monozygotic twins discordant for the Wiedemann-Beckwith syndrome.

Monozygotic twins discordant for the Wiedemann-Beckwith syndrome (WBS) were studied by cytogenetic and molecular methods to determine if a genetic lesion could be detected in the affected child. Probes known to be localized on the short arm of chromosome 11 and a low copy-repetitive probe were used. No genetic lesions could be ascertained in normal or affected tissue obtained from the WBS twin.

An expressed beta-tubulin gene, TUBB, is located on the short arm of human chromosome 6 and two related sequences are dispersed on chromosomes 8 and 13.

The chromosomal assignments of an expressed beta-tubulin gene and two related sequences have been determined by Southern blot analysis of DNA from a panel of human x Chinese hamster somatic cell hybrids cleaved with Hind III or EcoRI. Probes containing the 3' untranslated regions of the expressed gene M40 and of pseudogene 21 beta were used to localize the M40 sequence (gene symbol TUBB) to chromosome 6 region 6p21----6pter, the 21 beta pseudogene (TUBBP1) to chromosome 8 region 8q21----8pter and a third related sequence (TUBBP2) to chromosome 13. Asynteny of expressed genes and related processed pseudogenes has now been demonstrated for several gene families.

Regional assignments of three polymorphic DNA segments on human chromosome 15.

Hybridization of probe pDP151 (locus D15S2) to genomic human DNAs digested with EcoRI revealed allelic restriction fragments 9 and 11 kilobase-pairs (kb) in length. Hybridization of pDP151 to EcoRI-digested DNAs from 21 Chinese hamster X human hybrid cell clones containing different subsets of human chromosomes demonstrated cosegregation of the 9 and 11 kb EcoRI fragments with human chromosome 15. D15S2 and two other polymorphic loci previously mapped to chromosome 15--D15S1 and D15S6--were localized to specific regions on human chromosome 15. Eight Chinese hamster X human somatic cell hybrid clones derived from a human donor heterozygous for a balanced translocation between chromosomes 15 and 22 [t(15;22)(q14;q13.3); Oliver et al, Cytogenet Cell Genet 22:503-510, 1978] were studied. After digestion of human and hybrid DNAs with HindIII and Southern blotting, pDP151 (D15S2) and pMS1-14 (D15S1) hybridized to fragments of 4 and 4.5 kb, respectively. Further, pMS1-14 (D15S1) and p9-1a (D15S6) hybridized to EcoRI fragments of 3.5 and 3.2 kb. All fragments cosegregated with the der(22) derivative chromosome containing region 15q14----15qter. In situ hybridization of these probes to normal human chromosomes mapped the corresponding loci with greater precision: D15S1 to 15q15----15q21, D15S2 to 15q15----15q22, and D15S6 to 15q22----15q24.

Minute chromosomes replacing the Y chromosome carry Y-specific sequences by restriction fragment analysis and in situ hybridization.

Two unrelated males, a 43-year-old man with azoospermia and a 4-year-old boy with stature at the 10th centile, had similar karyotypes: 46,X,min. The minutes, present in all cells analyzed, stained weakly with G-, C-, and Q-banding methods. To elucidate their origin we used molecular techniques: In HaeIII digests of total genomic DNA from both individuals, no Y-specific reiterated sequences were detected. However, restriction fragment analysis with probe pDP31 demonstrated that the patients' DNA contained the Y-specific fragment. In situ hybridization with the same probe showed that these sequences were present on the minute chromosomes and have not been translocated elsewhere.

Localization of DNA sequences in region Xp21 of the human X chromosome: search for molecular markers close to the Duchenne muscular dystrophy locus.

Panels of somatic cell hybrid lines carrying various structural rearrangements of the human X chromosome short arm were analyzed with 21 X-chromosome-specific cloned DNA fragments. We mapped these molecular markers to five different regions of the short arm of the X chromosome. The results were confirmed by gene-dosage studies of human lymphoblasts with structurally abnormal X chromosomes. The ornithine transcarbamylase gene and four anonymous DNA sequences map within band Xp21, flanking the presumed locus for Duchenne muscular dystrophy.

Minor Xp21 chromosome deletion in a male associated with expression of Duchenne muscular dystrophy, chronic granulomatous disease, retinitis pigmentosa, and McLeod syndrome.

We are reporting a male patient who suffered from chronic granulomatous disease associated with cytochrome b-245 deficiency and McLeod red cell phenotype, Duchenne muscular dystrophy, and retinitis pigmentosa. On cytogenetic analysis, he seemed to have a very subtle interstitial deletion of part of band Xp21. Since it was impossible to know whether this material was truly deleted or inserted elsewhere in the genome, somatic cell and molecular studies were carried out. In somatic cell hybrids, the deleted X chromosome was isolated on a Chinese hamster background. Southern blot analysis with 20 single-copy probes, that had been mapped to the X short arm, led to the discovery of one (probe 754) that is missing from this patient's X chromosome and also from his total DNA. This proves that he, indeed, has a deletion rather than a balanced insertion. The results provide cytological mapping information for the X-linked phenotypes present in this patient. Furthermore, probe 754 recognizes a restriction fragment length polymorphism of high frequency that makes it the most powerful probe currently available for linkage studies with X-linked muscular dystrophy.