This study of living children with holoprosencephaly, the majority of whom are cytogenetically normal, provides new information on the subsample of children with a less severe phenotype.
For NPHP3, the phenotypic variability can be explained by the type of mutation with biallelic missense mutations resulting in the less severe phenotype of isolated nephronophthisis and two truncating mutations resulting in a Meckel-Gruber phenotype [18].
Sh3gl3 morphants (3 ng) had a less severe phenotype than hapln1b morphants.
This would explain why the Sp2lzn/lzn embryos display a markedly less severe phenotype when compared to Sp2null embryos.
Conversely, the individual or paired inactivation of FOXO1, FOXO3a or FOXO4 resulted in a less severe phenotype, supporting the idea of functional redundancy of these FOXO factors [26].
Thus, at the organ level co-expressing an activating and deactivating mutant allele could produce a less severe phenotype than either allele acting alone.
Given the less severe phenotype in Kcnma1−/− SCNs, it seems unlikely that BK channels transduce a significant component of VIP signaling.
Recently, a fourth yeast ESCRT-I subunit, Mvb12p, whose deletion results in a less severe phenotype characterized by a partial sorting defect was described [17] [20].
It has been proposed that this "mis-localised" protein may retain some of its copper transporting function, resulting in the less severe phenotype.
ACPA-negative RA is generally characterized by a less severe phenotype, and our observation that NSPR1 also associates with DAS28 score is intriguing.
Most of these studies have used the R6/1 mouse, which has a repeat length of approximately 115 CAG repeats, with a delayed onset of, and less severe, phenotype than the R6/2 mouse.
