BRCA2, is a gene with a critical role in DNA repair and homologous recombination in somatic cells. Patients with biallelic alterations develop Fanconi Anemia (FA), a severe life-threatening condition with pancytopenia and multiple malformations, while women with monoallelic alteration are at high risk to develop breast or ovarian cancer (up to 60%). Here, we surprisingly uncovered […]
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Genotype-phenotype correlations for pancreatic cancer risk in Dutch melanoma families with pathogenic CDKN2A variants
This study investigated the occurrence of pancreatic cancer in 172 familial melanoma families with a pathogenic CDKN2A variant. The CDKN2A gene encodes two distinct proteins (p16INK4a and p14ARF) and pathogenic variants can affect one or both. Individuals harbouring variants affecting p16INK4a are considered to be at increased risk for pancreatic cancer, but this study observed […]
Prevalence of BRCA1/BRCA2 pathogenic variation in Chinese Han population
Mutation in BRCA1 and BRCA2 genes increases the risk of breast and ovarian cancer. Identifying the mutation is a key to prevent and treat the mutation-caused cancer. China has the largest population of 1.4 billion in the world. By testing BRCA1/2 genes in 11,386 non-cancer Chinese Han individuals, we determined there is one BRCA mutation […]
Paternal 132 bp deletion affecting KCNQ1OT1 in 11p15.5 is associated with growth retardation but does not affect imprinting
A girl suffering from growth retardation inherited a small genetic deletion on chromosome 11p15.5 from her healthy father. By molecular genetic tests the region was characterised, and it turned out that the deletion affected the imprinted KCNQ1OT1 gene, i.e. a gene which is expressed only from the paternal allele. Since the father inherited the same […]
Hypomethylation of a centromeric block of ICR1 is sufficient to cause Silver-Russell syndrome
A major cause of an imprinting disorder, Silver-Russell syndrome (SRS), is the loss of DNA methylation (LOM) of imprinting control region 1 (ICR1) within the IGF2/H19 domain. ICR1-LOM on the paternal allele reduces IGF2 repression and makes H19 express biallelically. Majority of the patients showed consistent hypomethylation of ICR1; however, one exhibited LOM at the centromeric block of ICR1 but […]
Bi-allelic TTC5 variants cause delayed developmental milestones and intellectual disability
The overlapping and non-specific symptoms observed in patients with intellectual disability syndromes can make diagnosis difficult. Here, we report a new genetic intellectual disability syndrome in 8 patients characterized by moderate to severe intellectual disability, delayed verbal and motor milestones, and hypotonia. All patients have pathogenic variants in TTC5, a scaffold protein linked to many […]
A component of MICOS (APOO/MIC26) associated with a new X-linked mitochondrial myopathy, lactic acidosis, cognitive impairment and autistic features
Researchers from UK, Brazil and Italy identified the first family with a syndrome due to a mutation in APOO encoding MIC26, a component of the Mitochondrial Contact Site and Cristae Organizing System (MICOS). MICOS is considered the “mitoskeleton”, organizing the organelle cristae. The pathogenic change in MIC26 hits the hydrophobic region of the protein, compromising […]
‘Kinesinopathies’: emerging role of the kinesin family member genes in birth defects
Fetal structural anomalies can now be detected with increasing reliability during early pregnancy. The announcement of a serious conditionduring pregnancy or at birth is a devastating experience for the parents and the health professionals involved. The demand to find the cause is high to determine prognosis, clinical management and recurrence risks. We review the current […]
Evidence for polygenic and oligogenic basis of Australian sporadic amyotrophic lateral sclerosis
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease which has a high degree of genetic variability with dozens of different genes and hundreds of unique genetic alterations implicated in disease. We complied a comprehensive catalogue of these alterations totalling 853, and interrogated DNA sequences from 616 Australian patients without a family history of ALS […]
Update and audit of the St George’s classification algorithm of primary lymphatic anomalies: a clinical and molecular approach to diagnosis
The lymphatic system is a network of lymphoid organs and lymphatic vessels and is the body’s drain. Lymphatic disorders, such as lymphoedema and lymphatic malformations, result from a failure of the lymphatic system to transport fluid and immune cells from the body’s tissues for recycling. The discovery of genetic causes has changed the way we […]