Quantification of transmission risk in a male patient with a FLNB mosaic mutation causing Larsen syndrome: Implications for genetic counseling in postzygotic mosaicism cases.
Hum Mutat
; 38(10): 1360-1364, 2017 10.
Article
in En
| MEDLINE
| ID: mdl-28639312
ABSTRACT
We report the case of a male patient with Larsen syndrome found to be mosaic for a novel point mutation in FLNB in whom it was possible to provide evidence-based personalized counseling on transmission risk to future offspring. Using dideoxy sequencing, a low-level FLNB c.698A>G, encoding p.(Tyr233Cys) mutation was detected in buccal mucosa and fibroblast DNA. Mutation quantification was performed by deep next-generation sequencing (NGS) of DNA extracted from three somatic tissues (blood, fibroblasts, saliva) and a sperm sample. The mutation was detectable in all tissues tested, at levels ranging from 7% to 10% (mutation present in â¼20% of diploid somatic cells and 7% of haploid sperm), demonstrating the involvement of both somatic and gonadal lineages in this patient. This report illustrates the clinical utility of performing targeted NGS analysis on sperm from males with a mosaic condition in order to provide personalized transmission risk and offer evidence-based counseling on reproductive safety.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Osteochondrodysplasias
/
Filamins
/
Genetic Counseling
Type of study:
Etiology_studies
/
Prognostic_studies
/
Risk_factors_studies
Limits:
Adult
/
Humans
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Male
Language:
En
Journal:
Hum Mutat
Journal subject:
GENETICA MEDICA
Year:
2017
Type:
Article
Affiliation country:
United kingdom