Lp Tenkate

CARRIER SCREENING FOR CYSTIC FIBROSIS

INSTRUCTIONS FOR USE Physician Decision Support (PDS) is a lab ordering tool operated by BeaconLBS. This Clinical Guideline supports the Questions and Answers that appear in PDS for tests referenced in this document. UnitedHealthcare reserves the right, in its sole discretion, to modify its Clinical Guidelines as necessary. This Clinical Guideline is provided for informational purposes. It does not constitute a Medical Policy or medical advice.

Validation of the determination of Delta F508 mutations of the cystic fibrosis gene in over 11000 mouthwashes

Mouthwashes can be used as a DNA resource for mutation detection and, because collection and DNA isolation is simple and cheap, they could in particular, be used for large numbers of samples. To determine the failure rate (the proportion of mouth samples in which no PCR product was obtained) and the specificity of buccal epithelial cell mutation detection in large numbers of samples, we collected mouthwashes and blood samples from 11413 blood donors and tested the mouthwashes for the ΔF508 mutation, which has an estimated frequency of 75% among cystic fibrosis chromosomes in The Netherlands. Blood samples were tested for the ΔF508 mutations only if the mutation was identified in the mouthwash or in the case of a failure to obtain PCR products. The sensitivity of the test was determined in mouthwashes of 75 ΔF508 carriers known from earlier family studies. These samples were offered blindly between the mouthwashes of the blood donors. Both specificity and sensitivity of the mouthwash procedure were 100%. The overall failure rate was 5.6%. This large figure was caused mainly by insufficient rinsing of the mouth in one particular blood bank. Exclusion of the results of this blood bank reduced the failure rate to 1.8%. Our results also confirm that for a large number of samples the mouthwash procedure is suitable for mutation detection and, with proper instructions, can be used in community screening.

DOWN-SYNDROME - EFFECTS OF DEMOGRAPHIC-FACTORS AND PRENATAL-DIAGNOSIS ON THE FUTURE LIVEBIRTH PREVALENCE

In northwest European countries maternal age is increasing. This will lead to an increase of the prevalence of Down syndrome conceptuses. Meanwhile, the increased use of prenatal cytogenetic diagnosis (PCD) will lead to a decrease in the prevalence of Down syndrome among livebirths. We were interested to know what the result of these two opposite developments would be in the near future, and we describe here a model to quantify these processes and the resulting livebirth prevalence of Down syndrome. The model is demonstrated for The Netherlands from 1992 to 2001. The predicted livebirth prevalence for The Netherlands in 1992 is 1.36 per 1000. Demographic factors will cause an increase to 1.76 per 1000 in 2001 with present indications for PCD and a utilization ratio of 50%. An increase of the utilization ratio to 90% in 2001 will lead to a prevalence of 1.22 per 1000, a little less than the present prevalence. Alternative screening programs, including maternal serum screening, could lead to a further decrease of the livebirth prevalence. The model described here can be used for evaluation of the consequences of alternative forms of Down syndrome screening.

A BOY WITH POLAND ANOMALY AND FACIO-AURICULO-VERTEBRAL DYSPLASIA

Cobben JM, Van Essen AJ, McParland PC, Polman HA, ten Kate LP. A boy with Poland anomaly and facio‐auriculo‐vertebral dysplasia. Clin Genet 1992: 41: 105–107.

Prenatal prediction of spinal muscular atrophy - Experience with linkage studies and consequences of present SMN deletion analysis

With the localisation of the gene for the autosomal recessive forms of proximal spinal muscular atrophies (SMA) to the chromosomal region 5q13 and the later detection of homozygous deletions of the SMN gene located in this region, prenatal prediction of SMA has become feasible and is widely applied now. In our experience with 77 prenatal predictions of SMA, follow-up of the 39 liveborn children from these pregnancies never led to a false-negative result. Application of SMN deletion analysis has consequences for prenatal prediction of SMA. When the index patient has a homozygously deleted exon 7 of the SMN gene, prenatal prediction and interpretation of results are straightforward. In families in which no DNA from the index patient is available, prenatal detection of a homozygous SMN deletion may be considered almost proof of SMA in the fetus. Absence of a deletion, however, will not guarantee an unaffected child. A real problem exists if the index patient does not show a homozygous deletion of SMN exon 7. In such cases with nonhomozygous SMN deletions, one cannot be certain of 5q linkage and autosomal recessive inheritance until other SMN mutations are detected. This is an argument to abstain from prenatal diagnosis by linkage analysis in these families.

MENDELIAN PHENOTYPES IN THE NETHERLANDS

We report here a database listing Mendelian phenotypes described in the Netherlands and/or in populations originating from this country, and describe the results of a quantitative analysis of the database. The database is specifically directed at the presence, frequency and origin of the phenotypes. These are arranged according to their mode of inheritance: autosomal dominant (AD), autosomal recessive (AR) and X-linked. Only those phenotypes which have been reported in accessible sources were included. We entered 1,482 references up to January 1, 1991. At least 672 different loci were described in the Netherlands at this date: 321 (47.8%) AD, 283 (42.1%) AR and 68 (10.1%) X-linked. Almost 2.5% of all loci in our database have no comparable entry in McKusick [mendelian Inheritance in Man, ed 9. Baltimore, The Johns Hopkins University Press, 1990] (MIM). There is a significant difference (p < 0.01) according to the division into AD, AR, and X-linked phenotypes between our database and MIM, in which 61.7% of the phenotypes are AD, 31.5% AR and 6.8% X-linked. Dutch prevalence data for 38 monogenic disorders and 24 polymorphic systems are listed.

Family distances can reveal hidden consanguinity

Family distances, defined as summary measures of all possible geographic distances between birthplaces of paternal ancestors and birthplaces of maternal ancestors in a given generation, were compared in patients with autosomal recessive disorders and patients with Downs syndrome. In general, family distances in Downs syndrome patients were twice the family distances in patients with autosomal recessive disorders, even after the exclusion of rare disorders or cases with overt consanguinity. In modern, Western European societies grandparental and great‐grandparental family distances may be more appropriate measures of the effect of population structure than parental distance or parental consanguinity.

Serum dependency of cellular phenotype in mucopolysaccharidoses: The influence of autologous serum on metachromasia

SummaryMetachromasia of cultured fibroblasts from patients with mucopolysaccharidoses disappears if fetal calf serum in the culture medium is replaced by human serum, even if this serum is obtained from the patient himself.ZusammenfassungBei Zellen von Mucopolysaccharidose-Patienten verschwindet die Metachromasie in vitro, wenn im Kulturmedium das fetale Kalbserum durch menschliches Serum ersetzt wird, sogar wenn das Serum vom Patienten selbst stammt.