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 […]

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‘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 […]

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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 […]

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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 […]

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Prevalence and associated phenotypes of DUSP6, IL17RD and SPRY4 variants in a large Chinese cohort with isolated hypogonadotropic hypogonadism

Impaired development and function of GnRH neurons leads to isolated hypogonadotropic hypogonadism (IHH), characterized by delayed/absent puberty and/or infertility. IHH frequently associated with additional phenotypes, such as sensorineural deafness, coloboma, synkinesis, craniofacial abnormalities, and renal agenesis. In this report, we found DUSP6, an inhibitor of FGFR1, mutated in IHH in an autosomal dominant manner. IHH […]

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Diagnostic yield and clinical impact of exome sequencing in early-onset scoliosis (EOS)

Early-onset scoliosis (EOS), defined as clinical presentation of scoliosis before 10 years of age, can be associated with progressive pulmonary compromise and severe dysmorphic gross skeletal appearance if left untreated. In this study, Zhao et al. performed exome sequencing on a Chinese cohort of 447 patients with operative EOS and an US cohort of 13 […]

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15q11.2 deletion is enriched in patients with total anomalous pulmonary venous connection

15q11.2 has been associated a wide range of developmental such as neuropsychical diorders. In the study, we discovered that total anomalous pulmonary venous connection (TAPVC), A rare form of CHD, is significantly associated with 15q11.2 deletion. Using induced pluripotent stem (iPS) cells coupled with in vitro cardiomyocyte differentiation experiments, we showed that the iPS cells from the proband carrying […]

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Comprehensive genetic sequence and copy number analysis for Charcot-Marie-Tooth disease in a Canadian cohort of 2517 patients

Charcot-Marie-Tooth disease (CMT) is the most common hereditary neuromuscular disorder affecting more than 1 in 2500 people. Molecular defects that cause CMT are complex and involve large number of genes. This is the first Canadian study describing results of clinical genetic testing of nearly 3000 patients. This is also the largest patient cohort published to […]

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Understanding polygenic models, their development and the potential application of polygenic scores in healthcare

The use of genomic information in the form of polygenic scores as a predictive biomarker for common diseases has been an area of increasing interest. Methods applied in this field have evolved rapidly recently, with several methods proposed in generating these scores. An understanding of these methodological aspects is useful for considerations around implementation in […]

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Uptake of pre-symptomatic testing for BRCA1 and BRCA2 is age, gender, offspring and time dependent

Predictive BRCA1/2 testing, offered to healthy individuals after a BRCA1/2 gene change is identified in an affected family member, allows relatives to undergo cancer risk assessment and consider early cancer detection and risk-reduction strategies.  This study is the largest assessment of BRCA1/2 predictive testing uptake in close relatives, encompassing 5669 individuals from 1564 families, for […]

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