Abstract:
:Autosomal dominant polycystic kidney disease (ADPKD) is a heterogeneous genetic disorder caused by loss of function mutations of PKD1 or PKD2 genes. Although PKD1 is highly polymorphic and the new mutation rate is relatively high, the role of mosaicism is incompletely defined. Herein, we describe the molecular analysis of ADPKD in a 19-year-old female proband and her father. The proband had a PKD1 truncation mutation c.10745dupC (p.Val3584ArgfsX43), which was absent in paternal peripheral blood lymphocytes (PBL). However, very low quantities of this mutation were detected in the father's sperm DNA, but not in DNA from his buccal cells or urine sediment. Next generation sequencing (NGS) analysis determined the level of this mutation in the father's PBL, buccal cells and sperm to be ∼3%, 4.5% and 10%, respectively, consistent with somatic and germline mosaicism. The PKD1 mutation in ∼10% of her father's sperm indicates that it probably occurred early in embryogenesis. In ADPKD cases where a de novo mutation is suspected because of negative PKD gene testing of PBL, additional evaluation with more sensitive methods (e.g. NGS) of the proband PBL and paternal sperm can enhance detection of mosaicism and facilitate genetic counseling.
journal_name
Clin Genetjournal_title
Clinical geneticsauthors
Tan AY,Blumenfeld J,Michaeel A,Donahue S,Bobb W,Parker T,Levine D,Rennert Hdoi
10.1111/cge.12383subject
Has Abstractpub_date
2015-04-01 00:00:00pages
373-7issue
4eissn
0009-9163issn
1399-0004journal_volume
87pub_type
杂志文章abstract::Biochemical data are presented of a 29-year-old male, who shows progressive psychomotor retardation and a beta-galactosidase deficiency in leucocytes and cultured skin fibroblasts. Somatic cell hybridization studies show that this variant of GM1-gangliosidosis is based on a different gene mutation than is present in t...
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journal_title:Clinical genetics
pub_type: 杂志文章
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journal_title:Clinical genetics
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journal_title:Clinical genetics
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journal_title:Clinical genetics
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