Limits...
Mosaicism in von Hippel-Lindau disease: an event important to recognize.

Santarpia L, Sarlis NJ, Santarpia M, Sherman SI, Trimarchi F, Benvenga S - J. Cell. Mol. Med. (2007 Nov-Dec)

Bottom Line: The mosaic subject was found to have a cyst of the kidney and an angioma of the glans penis and had had surgery for a mandibular cyst and epididymal cystadenomas.Our results strongly suggest a complete and extensive clinical examination in the parents of each patient affected by an apparently de novo VHL germline mutation.We recommend performing a mutation screening of both parents of a proband with techniques that permit detection of low percentages of mosaicism before concluding that the proband has a de novo VHL mutation.

View Article: PubMed Central - PubMed

Affiliation: Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas, M. D. Anderson Cancer Center, Houston, TX, USA.

ABSTRACT
von Hippel-Lindau disease (VHL) is an autosomal dominant, familial neoplastic disorder with variable interfamilial and intrafamilial expression. VHL is characterized by pre-disposition to development of a combination of benign and malignant tumours affecting multiple organs. We provide molecular evidence of somatic mosaicism in nearly asymptomatic man whose daughter had VHL. The mosaic subject was found to have a cyst of the kidney and an angioma of the glans penis and had had surgery for a mandibular cyst and epididymal cystadenomas. Mosaicism could provide a genetic explanation for the clinical heterogeneity and variable severity of VHL. The real incidence of mosaicism is still unclear and the identification of mosaicism has important consequences in genetic counseling of VHL patients who appear to have de novo VHL mutations and should be considered when evaluating patients with isolated VHL-related tumours. Our results strongly suggest a complete and extensive clinical examination in the parents of each patient affected by an apparently de novo VHL germline mutation. We recommend performing a mutation screening of both parents of a proband with techniques that permit detection of low percentages of mosaicism before concluding that the proband has a de novo VHL mutation.

Show MeSH

Related in: MedlinePlus

MR image of the pro-band's brain.The arrow indicates a 1.6-cm-diameter right-sided supratentorial frontal meningioma.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC4401302&req=5

fig01: MR image of the pro-band's brain.The arrow indicates a 1.6-cm-diameter right-sided supratentorial frontal meningioma.

Mentions: The clinical features of the female pro-band have been reported in our previously published study [21], briefly, the young girl now 26 years old, underwent surgery at 11 years of age to resect a pheochromocytoma associated with hypertension. At age 18 years, she underwent further surgery to remove a pheochromocytoma in the contralateral adrenal gland and two concurrent paragangliomas of the abdominal aorta and urinary bladder. One year ago, she was also found to have a right-sided, extra-axial, 1.6-cm supratentorial frontal meningioma (Fig. 1). Post-operatively, neuroendocrine serum markers (plasma free metanephrines, chromogranin A, neuron- specific enolase, and gastrointestinal hormones carcinoembryonic antigen [CEA] and calcitonin) have remained negative. A family history obtained from her parents, one brother and one sister was uninformative, except for the father's history. The pro-band's relatives underwent physical examination.


Mosaicism in von Hippel-Lindau disease: an event important to recognize.

Santarpia L, Sarlis NJ, Santarpia M, Sherman SI, Trimarchi F, Benvenga S - J. Cell. Mol. Med. (2007 Nov-Dec)

MR image of the pro-band's brain.The arrow indicates a 1.6-cm-diameter right-sided supratentorial frontal meningioma.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4401302&req=5

fig01: MR image of the pro-band's brain.The arrow indicates a 1.6-cm-diameter right-sided supratentorial frontal meningioma.
Mentions: The clinical features of the female pro-band have been reported in our previously published study [21], briefly, the young girl now 26 years old, underwent surgery at 11 years of age to resect a pheochromocytoma associated with hypertension. At age 18 years, she underwent further surgery to remove a pheochromocytoma in the contralateral adrenal gland and two concurrent paragangliomas of the abdominal aorta and urinary bladder. One year ago, she was also found to have a right-sided, extra-axial, 1.6-cm supratentorial frontal meningioma (Fig. 1). Post-operatively, neuroendocrine serum markers (plasma free metanephrines, chromogranin A, neuron- specific enolase, and gastrointestinal hormones carcinoembryonic antigen [CEA] and calcitonin) have remained negative. A family history obtained from her parents, one brother and one sister was uninformative, except for the father's history. The pro-band's relatives underwent physical examination.

Bottom Line: The mosaic subject was found to have a cyst of the kidney and an angioma of the glans penis and had had surgery for a mandibular cyst and epididymal cystadenomas.Our results strongly suggest a complete and extensive clinical examination in the parents of each patient affected by an apparently de novo VHL germline mutation.We recommend performing a mutation screening of both parents of a proband with techniques that permit detection of low percentages of mosaicism before concluding that the proband has a de novo VHL mutation.

View Article: PubMed Central - PubMed

Affiliation: Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas, M. D. Anderson Cancer Center, Houston, TX, USA.

ABSTRACT
von Hippel-Lindau disease (VHL) is an autosomal dominant, familial neoplastic disorder with variable interfamilial and intrafamilial expression. VHL is characterized by pre-disposition to development of a combination of benign and malignant tumours affecting multiple organs. We provide molecular evidence of somatic mosaicism in nearly asymptomatic man whose daughter had VHL. The mosaic subject was found to have a cyst of the kidney and an angioma of the glans penis and had had surgery for a mandibular cyst and epididymal cystadenomas. Mosaicism could provide a genetic explanation for the clinical heterogeneity and variable severity of VHL. The real incidence of mosaicism is still unclear and the identification of mosaicism has important consequences in genetic counseling of VHL patients who appear to have de novo VHL mutations and should be considered when evaluating patients with isolated VHL-related tumours. Our results strongly suggest a complete and extensive clinical examination in the parents of each patient affected by an apparently de novo VHL germline mutation. We recommend performing a mutation screening of both parents of a proband with techniques that permit detection of low percentages of mosaicism before concluding that the proband has a de novo VHL mutation.

Show MeSH
Related in: MedlinePlus