For all six genes, we tested a complete deletion of the identified gene and found the same suppression phenotype, suggesting that all of the insertion mutations cause null phenotypes.
All mutations causing an NHS phenotype are null mutations predicted to produce no functional protein.
Each of these genes have multiple sequence-indexed mutations that disrupt exon sequences and are likely to cause null alleles [ 43].
In contrast, Drosophila csp null mutations cause 95% embryonic lethality, with the few flies surviving to adulthood being extremely sick and short lived (11, 12).
Although LAMB2 null mutations cause the full syndromic phenotype of Pierson syndrome, certain LAMB2 missense mutations, including R246Q and C321R, which are located in the LN or LEa domain of LAMB2 respectively, cause CNS with mild extrarenal features [ 48].
In model organisms, KIAA0586 null mutations cause failure of basal body docking and loss of cilia, leading to early embryonic lethal phenotypes (Davey et al., 2006; Bangs et al., 2011; Ben et al., 2011; Stephen et al., 2013).
Moreover, during mouse development, p53 null mutations cause a high frequency of neural tube defects and lethality that preferentially affects female embryos [ 50, 51], and interestingly, this sex difference appears to result from the number of X chromosomes rather than the presence or absence of the Y [ 52].
Although a clear Troyer syndrome diagnosis is difficult to reach in young subjects due to the variability and mildness of their symptoms, direct comparison of clinical features showed that the Omani cohort closely resembled the age-matched Amish Troyer syndrome group (Amish I), suggesting that SPG20 null mutations cause a well-defined phenotype.
These authors concluded that NPHP3-null mutations cause renal-hepaticpancreatic dysplasia.
We PCR-amplified and sequenced the rpoS gene from strains M114 and M646 to identify the mutation causing the RpoS-null phenotype.
