Clinical and genetic findings in TRPM1-related congenital stationary night blindness.

Purpose: Congenital stationary night blindness (CSNB) is a heterogeneous group of Mendelian retinal disorders that present in childhood. Biallelic variants altering the protein-coding region of the TRPM1 gene are one of the commonest causes of CSNB. Here, we report the clinical and genetic findings in 10 unrelated individuals with TRPM1-retinopathy.

Bi-allelic mutation of CTNNB1 causes a severe form of syndromic microphthalmia, persistent foetal vasculature and vitreoretinal dysplasia.

Background: Inherited vitreoretinopathies arise as a consequence of congenital retinal vascularisation abnormalities. They represent a phenotypically and genetically heterogeneous group of disorders that can have a major impact on vision. Several genes encoding proteins and effectors of the canonical Wnt/β-catenin pathway have been associated and precise diagnosis, although difficult, is essential for proper clinical management including syndrome specific management where appropriate.

Clinical and genetic variability in children with partial albinism.

Individuals who have ocular features of albinism and skin pigmentation in keeping with their familial background present a considerable diagnostic challenge. Timely diagnosis through genomic testing can help avert diagnostic odysseys and facilitates accurate genetic counselling and tailored specialist management. Here, we report the clinical and gene panel testing findings in 12 children with presumed ocular albinism.

Molecular findings from 537 individuals with inherited retinal disease.

Background: Inherited retinal diseases (IRDs) are a clinically and genetically heterogeneous set of disorders, for which diagnostic second-generation sequencing (next-generation sequencing, NGS) services have been developed worldwide.

Methods: We present the molecular findings of 537 individuals referred to a 105-gene diagnostic NGS test for IRDs. We assess the diagnostic yield, the spectrum of clinical referrals, the variant analysis burden and the genetic heterogeneity of IRD.

Explaining Mendelian inheritance in genetic consultations: an IPR study of counselor and counselee experiences.

The explanation of Mendelian inheritance is a key component of most genetic counselling consultations, yet no evidence base exists for this area of practice. This qualitative study used Interpersonal Process Recall (IPR) to explore how information about X-linked inheritance is provided and received in genetic counseling. Twelve consultations involving two senior genetic counselors and 21 counselees were videotaped.

The molecular genetics of breast cancer: the contribution of comparative genomic hybridization.

Comparative genomic hybridization (CGH) has been the technique of choice over the last 10 years for mapping DNA copy number changes in human tumors. Here we review the literature to demonstrate how CGH has contributed to the comprehension of molecular aspects of breast tumorigenesis. At least two distinct molecular pathways of breast cancer have been characterized that show a strong correlation with histological grade.

Molecular evolution of breast cancer.

Molecular analysis of invasive breast cancer and its precursors has furthered our understanding of breast cancer progression. In the past few years, new multi-step pathways of breast cancer progression have been delineated through genotypic-phenotypic correlations. Nuclear grade, more than any other pathological feature, is strongly associated with the number and pattern of molecular genetic abnormalities in breast cancer cells.

Distribution and significance of 14-3-3sigma, a novel myoepithelial marker, in normal, benign, and malignant breast tissue.

14-3-3sigma is a candidate tumour suppressor gene transactivated by p53 in response to DNA damage. In gene expression analysis of normal luminal and myoepithelial cells, 14-3-3sigma was preferentially expressed by myoepithelial cells. This study has analysed the immunohistochemical distribution and subcellular localization of 14-3-3sigma in normal breast tissue and in a large series of benign and malignant breast lesions on whole tissue sections and by tissue microarray.

The diagnosis and management of pre-invasive breast disease: pathology of atypical lobular hyperplasia and lobular carcinoma in situ.

The term lobular neoplasia refers to a spectrum of lesions featuring atypical lobular hyperplasia and lobular carcinoma in situ (LCIS). The histopathological characteristics of these lesions are well documented. What is less well understood is the management implications of a patient diagnosed with LCIS; treatment regimes vary and are somewhat controversial.