Mutation screening in Borjeson-Forssman-Lehmann syndrome: identification of a novel de novo PHF6 mutation in a female patient.
BACKGROUND
Börjeson-Forssman-Lehmann syndrome (BFLS; MIM 301900) is an infrequently described X linked disorder caused by mutations in PHF6, a novel zinc finger gene of unknown function.


OBJECTIVE
To present the results of mutation screening in individuals referred for PHF6 testing and discuss the value of prior X-inactivation testing in the mothers of these individuals.


RESULTS
25 unrelated individuals were screened (24 male, one female). Five PHF6 mutations were detected, two of which (c.940A-->G and c.27_28insA) were novel. One of these new mutations, c.27_28insA, was identified in a female BFLS patient. This was shown to be a de novo mutation arising on the paternal chromosome. This is the first report of a clinically diagnosed BFLS female with a confirmed PHF6 mutation. In addition, the X-inactivation status of the mothers of 19 males with suggested clinical diagnosis of BFLS was determined. Skewed (> or =70%) X-inactivation was present in five mothers, three of whom had sons in whom a PHF6 mutation was detected. The mutation positive female also showed skewing.


CONCLUSIONS
The results indicate that the success of PHF6 screening in males suspected of having BFLS is markedly increased if there is a positive family history and/or skewed X-inactivation is found in the mother.
Department of Genetic Medicine, Women's and Children's Hospital, University of Adelaide, Adelaide, Australia.
J
J
Crawford
K M
KM
Lower
R C M
RC
Hennekam
H
H
Van Esch
A
A
Mégarbané
S A
SA
Lynch
G
G
Turner
J
J
Gécz
D000015:Abnormalities, Multiple / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D017931:DNA Primers; D005260:Female; D006580:Genetic Carrier Screening; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics*; D008297:Male; D009154:Mutation; D012097:Repressor Proteins; D025064:Sex Chromosome Disorders / Q000235:genetics*; D016335:Zinc Fingers / Q000235:genetics
D002352:Carrier Proteins; D017931:DNA Primers; C502542:PHF6 protein, human; D012097:Repressor Proteins