Sorted By Test Name - Mayo Medical Laboratories

9862
VWD2N
81662
contrast, nonsense or frameshift mutations that disrupt overall VHL protein structure and large deletions
are associated with early clinical presentation and increased age-related risks for retinal angioma and
cRCC.
Useful For: Diagnosis of suspected von Hippel-Lindau disease, when familial mutations have been
previously identified Screening presymptomatic members of von Hippel-Lindau families, when familial
mutations have been previously identified Tailoring optimal tumor-surveillance strategies for patients,
when used in conjunction with phenotyping, when familial mutations have been previously identified
Interpretation: All detected alterations will be evaluated according to American College of Medical
Genetics and Genomics (ACMG) recommendations.(1) Variants will be classified based on known,
predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or
known significance.
Reference Values:
An interpretive report will be provided.
Clinical References: 1. Richards CS et al: ACMG Recommendations for standards for interpretation
and reporting of sequence variations: Revisions 2007. Genet Med 2008:10[4]:294-300 2. Online
Mendelian inheritance in Man-OMIM: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=193300 3.
Universal Mutation database-UMD-VHL mutations database page: http://www.umd.be:2020/ 4. Maher
ER, Kaelin WG Jr: von Hippel-Lindau disease (Reviews in Molecular Medicine). Medicine
1997;76:381-391 5. Pack SD, Zbar B, Pak E, et al: Constitutional von Hippel-Lindau (VHL) gene
deletions detected in VHL families by fluorescence in situ hybridization. Cancer Res 1999;59:5560-5564
6. Richards FM: Molecular pathology of von Hippel-Lindau disease and the VHL tumor suppressor gene.
Expert Rev Mol Med 2001;3:1-27 7. Hes FJ, Hoppener JWM, Lips CJM: Clinical review 155:
pheochromocytoma in von Hippel-Lindau disease. J Clin Endocrinol Metab 2003;88:969-974 8. Ong KR,
Woodward ER, Killick P, et al: Genotype-phenotype correlations in von Hippel-Lindau disease. Hum
Mutat 2007;28:143-149
Von Kossa's Stain for Calcium
Useful For: Metal substitution technique for demonstration of calcium.
Reference Values:
The laboratory will provide a pathology consultation and stained slide.
von Willebrand Disease 2N (Subtype Normandy), Blood
Clinical Information: Hemophilia A and von Willebrand disease (vWD) are bleeding disorders
caused by quantitative or qualitative defects in factor VIII (FVIII) or von Willebrand factor (vWF),
respectively, and constitute 2 of the most common bleeding disorders. Hemophilia A is inherited as an
X-linked recessive disorder while most subtypes of vWD are inherited as autosomal dominant disorders.
vWF plays 2 essential roles in hemostasis. vWF mediates platelet adhesion to damaged blood vessel walls
and vWF is a carrier protein for FVIII. Noncovalent binding of FVIII to vWF is necessary for normal
survival of FVIII in the blood circulation. In patients with severe vWD, the circulating half-life of
endogenous or infused FVIII is shortened. Mutations within the vWF gene regions encoding for the FVIII
binding domain of vWF may produce a phenotype of isolated FVIII "deficiency" associated with a
clinically mild-to-moderate bleeding disorder which may be misdiagnosed as HA. This mild vWD
phenotype was first described in patients from the Normandy region of France, vWD Normandy (vWD
Type 2N). vWD Type 2N inheritance pattern is autosomal recessive. In an international survey, vWD
Normandy was detected in 58 (4.8%) of 1,198 patients previously diagnosed as having mild hemophilia
A. Three vWF gene mutations (vWF Thr791Met, Arg816Trp, and Arg854Gln) accounted for 96% of
patients with mutations in the FVIII binding domain of vWF.(3) Patients who are homozygous for 1 of the
3 common mutations have reduced levels of FVIII activity, whereas patients who are heterozygous
typically have normal FVIII activity. However, patients who are heterozygous for 1 of the 3 common
vWD Type 2N mutations may have decreased FVIII activity in the presence of a second (compound
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