Further delineation of the phenotype of chromosome 14q13 deletions: (positional) involvement of FOXG1 appears the main determinant of phenotype severity, with no evidence for a holoprosencephaly locus.
BACKGROUND
Deletions including chromosome 14 band q13 have been linked to variable phenotypes. With current molecular methods the authors aim to elucidate a genotype-phenotype correlation by accurately determining the size and location of the deletions and the associated phenotype.


METHODS
Here the authors report the molecular karyotyping and phenotypic description of seven patients with overlapping deletions including chromosome 14q13.


RESULTS
The authors show that deletions including 14q13 result in a recognisable phenotype mainly due to haploinsufficiency of two genes (NKX2-1, PAX9). FOXG1 (on chromosome band 14q12) involvement seems to be the main determinant of phenotype severity. The patients in this study without FOXG1 involvement and deletions of up to 10 Mb have a relatively mild phenotype. The authors cannot explain why some patients in literature with overlapping but smaller deletions appear to have a more severe phenotype. A previously presumed association with holoprosencephaly could not be confirmed as none of the patients in this series had holoprosencephaly.


CONCLUSIONS
FOXG1 appears the main determinant of the severity of phenotypes resulting from deletions including 14q13. The collected data show no evidence for a locus for holoprosencephaly in the 14q13 region, but a locus for agenesis of the corpus callosum cannot be excluded.
Center for Human and Clinical Genetics, Leiden University Medical Center, Albinusdreef 2, Postbus 9600, Leiden 2300 RC, The Netherlands. santen@lumc.nl
Gijs W E
GW
Santen
Yu
Y
Sun
Antoinet C J
AC
Gijsbers
Aurore
A
Carré
Maureen
M
Holvoet
Arie van
Av
Haeringen
Saskia A J
SA
Lesnik Oberstein
Akemi
A
Tomoda
Hiroyo
H
Mabe
Michel
M
Polak
Koenraad
K
Devriendt
Claudia A L
CA
Ruivenkamp
Emilia K
EK
Bijlsma
D000328:Adult; D002648:Child; D002872:Chromosome Deletion; D002874:Chromosome Mapping; D002883:Chromosomes, Human, Pair 14; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics*; D057895:Haploinsufficiency; D016142:Holoprosencephaly / Q000235:genetics*; D006801:Humans; D007231:Infant, Newborn; D007621:Karyotyping; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics; D051764:PAX9 Transcription Factor / Q000235:genetics; D010641:Phenotype; D017422:Sequence Analysis, DNA; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors / Q000235:genetics
C090173:FOXG1 protein, human; D051858:Forkhead Transcription Factors; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D051764:PAX9 Transcription Factor; C497323:PAX9 protein, human; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors