A low-grade astrocytoma in a sixteen-year-old boy with a 7q11.22 deletion.

We report a patient with developmental delay due to germline AUTS2 mutation who developed a low-grade astrocytoma. While the contribution of this mutation to the pathogenesis of the tumor is not known at this time, a role of AUTS2 in deregulation of PRC1 can be a part in tumorigenesis of a brain tumor.

Asymmetric polymicrogyria and periventricular nodular heterotopia due to mutation in ARX.

Mutations in the ARX gene, at Xp22.3, cause several disorders, including infantile spasms, X-linked lissencephaly with abnormal genitalia (XLAG), callosal agenesis and isolated intellectual disability. Genotype/phenotype studies suggested that polyalanine tract expansion is associated with non-malformative phenotypes, while missense and nonsense mutations cause cerebral malformations, however, patients with structural normal brain and missense mutations have been reported. We report on a male patient born with cleft lip and palate who presented with infantile spasms and hemiplegia. MRI showed agenesis of corpus callosum (ACC), an interhemispheric cyst, periventricular nodular heterotopia (PVNH), and extensive left frontal polymicrogyria (PMG). Sequencing of the ARX gene in the patient identified a six basepair insertion (c.335ins6, exon 2). The insertion leads to a two-residue expansion of the first polyalanine tract and was described previously in a family with non-syndromic X-linked mental retardation. To our knowledge, ARX mutation causing PMG and PVNH is unique, but the spasms and ACC are common in ARX mutations. Clinicians should be aware of the broad clinical range of ARX mutations, and further studies are necessary to investigate the association with PMG and PVNH and to identify possible modifying factors.

Infertility, assisted reproduction technologies and imprinting disturbances: a Dutch study.

BACKGROUND: Evaluation of relationships between assisted reproduction technologies (ART), fertility problems and disorders caused by disturbed genetic imprinting such as Angelman syndrome (AS) and Beckwith-Wiedemann syndrome (BWS). METHODS: A nation-wide questionnaire survey was performed regarding ART in families with a child with AS, BWS or Prader-Willi syndrome (PWS) including questions on fertility. Molecular data on the genetic disorder in affected children were gathered. RESULTS: Of the 220 affected children in this study, 14 (6.4%) were born following any form of ART compared with 83 818 (2.1%) in the Dutch population. Of AS, PWS or BWS children 15 (6.8%) were born after a fertility problem (Time To Pregnancy > 12 months, no forms of ART) compared to 141,340 (3.5%) in the Dutch population. Maternal age in the individual syndromes was higher than in the Dutch population. Families with affected children were three times more likely to experience fertility problems than the general population. All three syndromes were also individually associated with increased fertility problems in the families. CONCLUSIONS: After correction for the increased fertility problems of the parents, there is no increased incidence of ART related birth of AS, PWS or BWS children. ART does not seem to have a direct effect on the increase of imprinted diseases.