Purpose Neural tube defects (NTDs) occur in 1:1000 births.
The etiology is complex, with the influence of environmental
and genetic factors. Environmental factors, such as folate deficiency,
diabetes, or hypoxia strongly contribute to the occurrence
of NTD. Also, there is a strong genetic contribution to
NTD, as highlighted by the number of genes so far identified
in several different developmental pathways usually altered in
NTD. Each gene identified so far accounts for a small percentage
of all NTD cases, indicating a very high heterogeneity.
Methods Exome sequencing was performed in seven sporadic
patients with severe mielomeningocele. Novel coding variants
shared by two or more patients were selected for further
Results We identified in two unrelated patients two different
variants in TNIP1, a gene not previously involved in NTD
whose main role is downregulation of the NF-kB pathway.
One variant, c.1089T>G (p.Phe363Leu), is de novo, whereas
the c.1781C>T (p.Pro594Leu) is absent in the mother, but
could not be tested in the father, as he was unavailable. The
latter variant is a very rare variant in the ExAC database.
Conclusions These findings suggest that TNIP1 is a new potential
predisposing gene to spina bifida (SB) and its pathway
needs to be investigated in human NTD in order to confirm its
role and to plan appropriate counseling to families.
|Numero di pagine||7|
|Rivista||CHILDS NERVOUS SYSTEM|
|Stato di pubblicazione||Pubblicato - 2016|