BRCA1/2 mutations are responsible for a significant portion of hereditary breast and ovarian cancers. Identifying patients with BRCA1/2 mutations allows for gene-directed surveillance and intervention. The Manchester Scoring System (MSS) is a quick and easy algorithm to identify patients with a likelihood of having a BRCA1/2 mutation. Recently, a third iteration of MSS (MSS3), validated […]
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Cole-Carpenter syndrome due to recurrent P4HB variant
In 1987, Cole and Carpenter reported two infants with multiple fractures and deformities of bone, with a skeletal phenotype similar to severe brittle bone disease. They were reported to have normal intelligence. This came to known as Cole-Carpenter syndrome (CCS). With advances in genetic screening, in 2015, these two patients were reported to have changes […]
Two patients with MIRAGE syndrome lacking haematological features: role of somatic second-site reversion SAMD9 mutations
MIRAGE syndrome is a life-threatening congenital disorder caused by deleterious SAMD9 mutations. In MIRAGE syndrome patients, multiple organ systems, including the haematopoietic system, are affected. We experienced two atypical MIRAGE syndrome patients who did not have any haematopoietic problems. In leukocyte DNA samples of the two patients, not only a deleterious SAMD9 mutation, but also […]
Pediatric Ovarian Tumours and Their Associated Cancer Susceptibility Syndromes
Ovarian cancers arising in children and adolescents are rare events and can be associated with various cancer predisposition syndromes (i.e., genetic conditions that heighten the risk of developing cancers throughout life). Although germ cell tumours are the most frequent subtype of ovarian cancer seen in the pediatric age group, a multitude of other tumours can […]
Genome-wide association study of telomere length among South Asians identifies a second RTEL1 association signal
Telomeres are DNA-protein complexes that protect chromosome ends. Leukocyte telomere length (LTL) is a potential biomarker of aging and risk for age-related disease. Prior genome-wide association (GWA) studies have identified 10 inherited genetic variants that influence LTL in populations of European ancestry. However, there is evidence of considerable population differences in LTL. In this GWA […]
Homozygous mutation in CEP19, a gene mutated in morbid obesity, in Bardet-Biedl syndrome with predominant postaxial polydactyly
Bardet-Biedl syndrome (BBS) presents a complex phenotype. We discovered that CEP19 gene is defective in a Pakistani family with many members having postaxial polydactyly plus variable other clinical features including rod-cone dystrophy, obesity, intellectual disability, renal malformation, developmental delay, dental anomalies, speech disorder and enlarged fatty liver. We also found different combinations of modifier alleles […]
New Bone Dysplasia with Cloudy Cornea and Intellectual Disability caused by homozygous PLCB3 variants
Ben-Salem, Robbins et al. reports a new form of syndromic bone dysplasia in two Emirati first cousins. This new syndrome includes profound limb shortening with spine and pelvis abnormalities, corneal clouding, and intellectual disability. Homozygosity mapping in the family localized the genetic cause to cytogenetic band 11q12.1-q13.1. Whole exome sequencing identified a homozygous variant, c.2632G>T, […]
Genome-wide association study identified copy number variants associated with sporadic colorectal cancer risk
Colorectal Cancer (CRC) is the third most frequent cancer worldwide and associated with high mortality. We identified a rare structural or copy number variant region (CNVR) encompassing a chromatin remodeler (CHD8) and two common CNVRs encompassing an anti-phagocytic molecule (CD47) and two members of the RAS superfamily of GTPases (RERG/ARHGDIB) respectively in the human genome […]
A novel de novo dominant mutation in ISCU associated with mitochondrial myopathy
In our paper, we report the identification of a de novo mutation in ISCU in a young male presenting ptosis, severe muscle weakness, and marked exercise intolerance. The first mutation in ISCU was described almost 10 years in Swedish patients while the second mutation was found the following year. No additional mutation in ISCU has […]
GWAS on prolonged gestation (post-term birth): analysis of successive Finnish birth cohorts
Amongst 3 billion bases of DNA lurks some 10 million points of genetic variation, making us who we are as individuals. We identify genetic variants associated with being born later than expected. These variants are in non-coding regions of the DNA. The evidence indicates that they affect genes that are a long way away within […]