摘要:

AbstractWe describe 2 cases of DiGeorge anomaly with bilateral renal agenesis–one, who also had hemivertebrae, in an infant of an insulin–dependent diabetic mother (IDDM). In a review we identified 2 other instances of this combination, both in IDDMs. The currently accepted notion that DiGeorge anomaly and renal agenesis are developmental field defects, coupled with their coincidence in IDDM, suggests that this combination is an association. © 1994 Wiley‐Lis

ISSN:0148-7299    

DOI:10.1002/ajmg.1320500402

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

摘要:

AbstractSix familial cases of the Beemer–Langer syndrome (BLS) were analyzed to further elucidate the spectrum and frequency of anomalies observed in this disorder. Preaxial polydactyly was found in 3/6 affected sibs, and, therefore, its frequency previously may have been underestimated. Some patients, described as infants affected with the Majewski syndrome (MS) or “atypical” short rib‐poly‐dactyly conditions, may indeed have BLS. A high frequency of brain defects (16/26) and cleft tongue, oral frenula, and/or natal teeth (13/29) widens the list of typical findings in this syndrome. The specific type of tibial defect seems to be the most important discrimination of the MS and the BLS. © 1994 Wiley

ISSN:0148-7299    

DOI:10.1002/ajmg.1320500403

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

摘要:

AbstractWe report on 10 Japanese individuals from 3 families affected with Aarskog syndrome. Pulmonary stenosis and ventricular septal defect with spontaneous closure were detected respectively, in 2 of them as an uncommon finding. A review documented 169 non‐Japanese cases (2 with congenital heart defects), while of 30 Japanese individuals reported till now, 4 (including ours) had cardiac anomalies. We propose that this combination is not coincidental and that in all cases of Aarskog syndrome a cardiac evaluation is indicated. © 1994 Wiley‐Liss,

ISSN:0148-7299    

DOI:10.1002/ajmg.1320500404

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

摘要:

AbstractWe report on a newborn girl with duplication of 18q12.2→18qter and deficiency of 18p11.2→18pter which resulted from meiotic recombination of the maternal pericentric inversion, inv(18) (p11,2q12.2). Her clinical manifestations were compatible with those of partial trisomy 18q syndrome. We review the previously reported 9 cases in 8 families of rec(18) resulting from recombination of a parental pericentric inversion. © 1994 Wiley‐Lis

ISSN:0148-7299    

DOI:10.1002/ajmg.1320500405

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

摘要:

AbstractDuring the evolution of multicellularity and attendant processes of development, cholesterol played a key role in the formation of the plasma membrane and outer mitochondrial membrane of every cell in the organism. Later functions include pivotal involvement in steroid, bile acid, and vitamin D metabolism and myelination of the nervous system. In the CNS myelination does not begin until the third trimester, and subcortical myelination not until after birth. The cholesterol of the cell membrane of the ovum is maternally derived. It is not known when the zygote begins making its own cholesterol during morphogenesis and histogenesis, but it must occur early to keep up with the dramatic rate of cell division in the embryo. Thus, it is a startling surprise that human embryos and fetuses apparently able to synthesize little cholesterol (because of a presumed defect of the Δ5,7‐sterol, Δ7‐reductase that converts 7‐dehydrocholesterol (7‐DHC) into cholesterol) frequently live to term and, rarely, may be so mildly affected as to attend school with only mild MR. The discovery by G. Stephen Tint and his co‐workers of the apparent 7‐DHC reductase deficiency makes the RSH (Smith‐Lemli‐Opitz) syndrome the first true metabolic malformation syndrome. A teratological animal model which has been known for 30 years now appears applicable to the RSH/SLO syndrome. A multidisciplinary NICHD conference held on September 20–21, 1993 reviewed the numerous implications of this discovery and agreed unanimously that research in this field be given highest priority in order to better understand cholesterol synthesis in the mammalian brain, cholesterol transport from mother to embryo and fetus, pre‐and postnatal metabolic compensation in structure and function for a profound block in cholesterol synthesis, the nature of the blood–brain barrier for cholesterol, treatment of affected infants, children, and adults, structure and genetic specification of a 7‐DHC reductase enzyme (which has never been purified!) and its evolution, the variability of the syndrome and whether it is genetically homo‐ or heterogeneous, the population genetics of the RSH syndrome, possible selective advantages (or disadvantages) of heterozygotes, and means of newborn screening, carrier detection, and prenatal diagno

ISSN:0148-7299    

DOI:10.1002/ajmg.1320500406

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

ISSN:0148-7299    

DOI:10.1002/ajmg.1320500407

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

摘要:

AbstractThirty years after the publication of Smith et al. [1964: J Pediatr 64:210–217] of 3(4) cases of the RSH/SLO (“Smith‐Lemli‐Opitz”) syndrome and after the publication by Roux [1964: Arch Franç Pédiatr 21:451–464]on the teratogenic action of Triparanol, a defect of cholesterol metabolism was discovered by Tint and his co‐workers in the blood of the patients of Irons and Elias [Irons et al., 1993: Lancet 341:1414]. In this manner, the RSH syndrome has been identified as another metabolic multiple congenital anomalies/mental retardation (MCA/MR) syndrome (prototype Zellweger syndrome) in which deficient cholesterol synthesis must be held responsible for all parts of the syndrome, including blastogenetic and organogenetic malformations, minor anomalies, more or less severe abnormalities of CNS and PNS structure and function, postnatal failure to thrive, and, in some cases, stillbirth or infancy/childhood death. © 1994

ISSN:0148-7299    

DOI:10.1002/ajmg.1320500408

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

摘要:

AbstractWe report on four patients with the Smith‐Lemli‐Opitz (SLO) syndrome who appear to have a defect in cholesterol biosynthesis. The initial results of therapy of one of the patients with cholesterol and bile acids to correct her metabolic abnormalities are described. This finding provides a biochemical marker to help in the diagnosis of this syndrome, may provide insight into the pathogenesis of this disorder, and have therapeutic and prenatal diagnostic implications as well. © 1994 Wiley‐Lis

ISSN:0148-7299    

DOI:10.1002/ajmg.1320500409

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

摘要:

AbstractCholesterol is an enigmatic, essential metabolite. Breast milk contains significant quantities of cholesterol, yet human infants thrive on cholesterol‐free diets. Recommendations to lower serum cholesterol are widespread, yet low serum cholesterol is associated with poorly understood morbidity. Serum cholesterol is increased with diets high in fat, yet dietary cholesterol has relatively little effect on serum concentrations. Smith‐Lemli‐Opitz syndrome, marked with extremely low serum cholesterol, may serve as a human model for the evaluation of absorption and metabolism of dietary cholesterol. © 1994 Wiley‐L

ISSN:0148-7299    

DOI:10.1002/ajmg.1320500410

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

摘要:

AbstractThe developmental patterns of expression of HMG‐CoA reductase, farnesyl pyrophosphate synthase, cholesterol 7α‐hydroxylase, and LDL receptor were investigated using Northern blotting analysis to quantitate mRNA levels. It was found that HMG‐CoA reductase and farnesyl pyrophosphate synthase mRNA levels in brain reached peaks at age 4 days which correlates with the time of peak enzyme activity and the onset of rapid brain growth and myelination. In liver, HMG‐CoA reductase and cholesterol 7α‐hydroxylase mRNA both rose dramatically at weaning. This is consistent with the concept that de novo synthesized cholesterol is the preferred substrate for cholesterol 7α‐hydroxylase and may also be involved in the induction of the enzyme. In testes, HMG‐CoA reductase activity was highest at age 21 days and then declined, while LDL receptor mRNA levels rose from age 31 to 120 days. These studies suggest a major role for de novo cholesterol synthesis in developing brain, liver, and testes. © 199

ISSN:0148-7299    

DOI:10.1002/ajmg.1320500411

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY