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.
- Chromosome 14q13
- clinical genetics
- adrenal disorders
- pituitary disorders
- molecular genetics
- thyroid disease
- copy number
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Competing interests None.
Patient consent Obtained.
Ethics approval Most investigations were performed in the course of routine clinical care. In the remaining cases the molecular karyotyping was performed to delineate the exact size and location of a deletion already found by other methods. No new patient samples were required.
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement All CNV information is present in the paper. No additional data will be uploaded to repositories.
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