Holoprosencephaly (HPE) is the most common malformation of the human forebrain. Typical manifestations in affected patients include a characteristic pattern of structural brain and craniofacial anomalies. HPE may be caused by mutations in over 10 identified genes; the inheritance is traditionally viewed as autosomal dominant with highly variable expressivity and incomplete penetrance. We present the description of a family simultaneously segregating two novel variants in the HPE-associated genes, ZIC2 and GLI2, as well as the results of extensive population-based studies of the variant region in GLI2. This is the first time that multiple HPE-associated variants in these genes have been reported in one family, and raises important questions about how clinicians and researchers should view the inheritance of conditions such as HPE.

Download full-text PDF

Source
http://dx.doi.org/10.1002/ajmg.a.33903DOI Listing

Publication Analysis

Top Keywords

segregating novel
8
novel variants
8
zic2 gli2
8
holoprosencephaly family
4
family segregating
4
variants zic2
4
gli2 holoprosencephaly
4
holoprosencephaly hpe
4
hpe common
4
common malformation
4

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!