Diverse presentations of cutaneous mosaicism occur in CYLD cutaneous syndrome and may result in parent-to-child transmission.

Background: Clusters of rare cylindroma or spiradenoma tumors are a recurrent clinical presentation, yet conventional genetic testing results in individuals with these tumors are frequently normal.

Objective: To determine if genetic mosaicism accounts for such cases.

Methods: A study of 6 cases from a series of 55 patients who met criteria for diagnostic gene testing for pathogenic CYLD variants over a 5-year period (2012-2017) was performed.

Disrupted alternative splicing for genes implicated in splicing and ciliogenesis causes PRPF31 retinitis pigmentosa.

Mutations in pre-mRNA processing factors (PRPFs) cause autosomal-dominant retinitis pigmentosa (RP), but it is unclear why mutations in ubiquitously expressed genes cause non-syndromic retinal disease. Here, we generate transcriptome profiles from RP11 (PRPF31-mutated) patient-derived retinal organoids and retinal pigment epithelium (RPE), as well as Prpf31 mouse tissues, which revealed that disrupted alternative splicing occurred for specific splicing programmes. Mis-splicing of genes encoding pre-mRNA splicing proteins was limited to patient-specific retinal cells and Prpf31 mouse retinae and RPE.

Human-Specific NOTCH2NL Genes Affect Notch Signaling and Cortical Neurogenesis.

Genetic changes causing brain size expansion in human evolution have remained elusive. Notch signaling is essential for radial glia stem cell proliferation and is a determinant of neuronal number in the mammalian cortex. We find that three paralogs of human-specific NOTCH2NL are highly expressed in radial glia.

Microdeletion 1p35.2: a recognizable facial phenotype with developmental delay.

We describe two patients with microdeletion 1p35.2, intrauterine growth retardation, small stature, hypermetropia, hearing impairment and developmental delay. Both patients have long, myopathic facies, with fine eyebrows, small mouths and micrognathia.

Late-onset sacsinopathy diagnosed by exome sequencing and comparative genomic hybridization.

The molecular diagnosis of adult-onset autosomal recessive cerebellar ataxias remains challenging because of genetic heterogeneity. However, recently developed molecular genetic techniques will potentially revolutionize the diagnostic approach. Here we set out to define the genetic basis of the ataxia in two brothers with no molecular diagnosis.

3q26.33-3q27.2 microdeletion: a new microdeletion syndrome?

We describe three unrelated patients of European descent carrying an overlapping 3q26.33-3q27.2 microdeletion who share common clinical features: neonatal hypotonia, severe feeding problems, specific facial features, abnormal dentition, recurrent upper airways infections, developmental delay and severe growth impairment.

A case of mosaic trisomy 19q12-q13.2 with high BMI, macrocephaly, and speech delay: does USF2 determine size in the 19q phenotypes?

Hall et al. (2010) describe a boy with mosaic trisomy of the proximal part of 19q, with obesity, macrocephaly and global developmental delay. The patient is interesting with regard to his cytogenetic abnormality, which is smaller than those previously reported, and does not include the candidate obesity and insulin-resistance genes identified by other authors (Zung et al.

Neurogenic properties and a clinical relevance of multipotent stem cells derived from cord blood samples stored in the biobanks.

Several innovative therapies with human umbilical cord blood stem cells (SCs) are currently developing to treat central nervous system (CNS) diseases. It has been shown that cord blood contains multipotent lineage-negative (LinNEG) SCs capable of neuronal differentiation. Clinically useful cord blood samples are stored in different biobanks worldwide, but the content and neurogenic properties of LinNEG cells are unknown.

A de novo 4q34 interstitial deletion of at least 9.3 Mb with no discernible phenotypic effect.

Cytogenetically visible imbalances without phenotypic effect are still rare despite the extent of large-scale copy number variation in the normal population revealed by array CGH. Here we report on a phenotypically normal 30-year-old female with a de novo, cytogenetically visible, interstitial deletion of band 4q34. She was referred following three successive miscarriages, one of which was an intra-uterine death with subendocardial fibroelastosis and dilated cardiomyopathy.

8p23.1 duplication syndrome; a novel genomic condition with unexpected complexity revealed by array CGH.

The 8p23.1 deletion syndrome is established but not an equivalent duplication syndrome. Here, we report five patients; a de novo prenatal case and two families in which 8p23.

Immortalisation of human ovarian surface epithelium with telomerase and temperature-sensitive SV40 large T antigen.

Epithelial ovarian cancer is the most common form of gynaecological malignancy. This lethal disease is thought to arise in ovarian surface epithelial (OSE) cells. The biology of these cells is not well understood, due to the limited amount of tissue that can be obtained from a single biopsy and their limited life span in culture.