Commentary

Trinucleotide repeats not the only cause of anticipation

Familial aggregation of testicular germ cell tumor (TGCT) has been reported, but it is unclear if familial TGCT represents a unique entity with distinct clinicopathologic characteristics. Here we describe a collection of familial TGCT cases from an international consortium, in an effort to elucidate any clinical characteristics that are specific to this population.

Families with ≥2 cases of TGCT enrolled at 18 of the sites participating in the International Testicular Cancer Linkage Consortium were included. We analyzed clinicopathologic characteristics of 985 cases from 461 families.

A majority (88.5%) of families had only 2 cases of TGCT. Men with seminoma (50% of cases) had an older mean age at diagnosis than nonseminoma cases (P = 0.001). Among individuals with a history of cryptorchidism, TGCT was more likely to occur in the ipsilateral testis (κ = 0.65). Cousin pairs appeared to represent a unique group, with younger age at diagnosis and a higher prevalence of cryptorchidism than other families.

Clinicopathologic characteristics in these familial TGCT cases were similar to those generally described for nonfamilial cases. However, we observed a unique presentation of familial TGCT among cousin pairs. Additional studies are needed to further explore this observation.

Although the evidences for the phenomenon of “anticipation” and parental “imprinting” have been shown in schizophrenia, they are inconclusive. The purpose of this study was to test these hypotheses by examining three successive generations.

58 schizophrenic patients who had their maternal or paternal parent or grandparent, or both, affected with schizophrenia or related disorders were analyzed. Chi-square test was used to assess the association of the sex of the parent with more than one of the affected proband families. The differences in the age of onset of the illness between the successive three generations was calculated using the t-test.

In comparison to mothers’ affected families, a large proportion of the father side affected families had more than one of their offspring affected with the illness. The age of onset in probands was lower in comparison to that of those on the parental side and the difference was more significant when the paternal side was affected. Interestingly, when the age of onset in the grandparents was compared with either of the parental sides of the probands no difference emerged, indicating lack of support from this study for the theory of anticipation. At any rate, the age of onset of probands was significantly lower in comparison to that of the paternal grandfather side. Further, skipping of a generation in the process of transmission was noted in some families.

It is hard to ignore our findings that suggest paternal side transmission.

Paroxysmal kinesigenic dyskinesia (PKD) is a rare neurologic inherited disease with heterogeneity. Autosomal dominant (AD) is the common inherited mode. There have been two loci mapped to 16 chromosome for PKD. However, no gene responsible for it has been identified so far. We collected 6 pedigrees from Chinese mainland. There were 122 members in all, including 26 affected. According to New diagnostic criteria of Bruno, they were diagnosed as pure PKD. From the clinic data, we found that the onset age was earlier and the severity was increasing in the subsequent generations in 4 pedigrees of them, which suggested genetic anticipation. Linkage analysis was applied in 2 of these pedigrees. The maximum LOD score and NPL score were negative. The followed haplotypes analysis excluded the PKD locus in both families from chromosome 16, providing evidence for a novel locus.