You don't need to be signed in to read BMJ Blogs, but you can register here to receive updates about other BMJ products and services via our site.

An interstitial deletion within 9p21.3 and extending beyond CDKN2A predisposes to melanoma, neural system tumours and possible haematological malignancies

5 Feb, 16 | by hqqu

We report a 52 year old Caucasian male with a referring diagnosis of neurofibromatosis type 1 (NF1), due to multiple nerve sheath tumors, who was subsequently found to have a large deletion spanning CDKN2A,the major melanoma susceptibility gene, and including approximately 24 additional genes underlying his strong family history of melanoma and neural system tumors.  Traditional Sanger sequencing initially missed the CDKN2A deletion.  Knowledge regarding the association of melanoma and neural system tumors, though, informed additional testing that permitted the detection of the large deletion and now provides an accurate test for relatives at potential risk for cancer.  A clinical team was assembled and a management strategy developed to address the unusual constellation of tumors exhibited by family members, not all of which, at this time, have been proven to relate to the large familial deletion. (By Dr. Maria J. Baker, )

HSP110 T17 simplifies and improves the microsatellite instability testing in patients with colorectal cancer

1 Feb, 16 | by hqqu

Every colorectal cancer (CRC) patient should be tested for Microsatellite Instability (MSI), as a first screen for Lynch syndrome (LS). Recently, clinical benefit from immune checkpoint blockade was reported in metastatic MSI CRCs. Hence, there is a high level of interest in studying the MSI phenotype as a potential prognostic and predictive biomarker in CRC patients. In the present work, we demonstrate that a new marker, HT17, simplifies and improves the current standard molecular methods for detecting MSI in colon tumor samples. We believe there is a strong rationale to use HT17 when screening for MSI in CRC. (By Ada Collura, )

Multigene testing of moderate-risk genes: be mindful of the missense

19 Jan, 16 | by hqqu

What fraction of early-onset breast cancer patients inherited a clinically actionable moderate-risk genotype? To estimate this, we applied both multi-gene mutation screening and SNP genotyping to 1,297 early onset breast cancer cases and 1,121 controls. Mutation screening revealed that 2.1% of the cases carried an obviously pathogenic protein-truncating variant in one of nine moderate-risk genes, plus 5.4% carried a missense substitution with a high-probability of pathogenicity. In addition, 2.1% carried a notable excess of individually modest-risk SNPs. Thus, beyond mutations in high-risk genes such as BRCA1 and BRCA2, a further 9.6% of early onset cases inherited an actionable moderate-risk genotype. (By Erin Young, )

Disturbed mitochondrial and peroxisomal dynamics due to loss of MFF causes Leigh-like encephalopathy, optic atrophy and peripheral neuropathy

18 Jan, 16 | by hqqu

Mitochondria, “the powerhouses of the cells” are dynamic organelles which undergo continuous fission and fusion to maintain their diverse cellular functions. Mitochondrial fission factor MFF is a component of the fission machinery shared between mitochondria and peroxisomes. We for the first time present detailed clinical and functional data of three patients with loss of function mutations in MFF and affirm MFF as another disease gene, causing a defect of mitochondrial and peroxisomal homeostasis. Concerning the underlying pathomechanism the consequences of the organellar structural abnormalities still remain unclear and need to be clarified by further studies. (By Dr. Johannes Koch, )

Cystic cerebellar dysplasia and biallelic LAMA1 mutations: a lamininopathy associated with tics, obsessive compulsive traits and myopia due to cell adhesion and migration defects

13 Jan, 16 | by hqqu

Laminins are proteins that form a major component of basement membranes and extracellular matrix in human tissues. We have performed clinical and neuropsychiatric evaluation, and molecular analysis in patients with mutations in the LAMA1 gene that codes for the protein laminin-α1. We investigated the consequence of mutations in LAMA1 using nerve cells derived from stem cells and patients’ skin cells. Patients had cyctic cerebellar dysplasia, myopia, and retinal dystrophy, obsessive compulsive behaviors, tics, and anxiety. Skin cells had impaired adhesion, reduced migration, and abnormal morphology. Human neuronal cells without laminin-α1 showed abnormal cellular extension formation marking these cells potentially useful tools for disease modeling and drug discovery. (By Dr. Meral Gunay-Aygun, )

A Genetic Region Associated with Seizure Susceptibility is Identified in Wolf-Hischhorn Syndrome

8 Jan, 16 | by hqqu

Wolf-Hirschhorn syndrome (WHS) is a contiguous gene deletion syndrome involving variable size deletions of the short arm of chromosome 4. Approximately 90% of individuals with WHS have seizures. These seizures can be intractable and can seriously affect an individual’s quality of life, especially during childhood.


To study the genetic correlates of seizure susceptibility in WHS, we used a custom, high density chromosomal microarray platform designed for optimal detection of genomic changes associated with autism and neurodevelopmental disorders. By correlating the size and location of chromosome 4p deletions of forty-eight individuals with WHS with their seizure phenotypes, we identified a new genetic region located at the 4p terminus for seizure susceptibility. This region includes a potential candidate gene for seizure susceptibility, PIGG.


Future studies will involve the use of new computational and statistical methods to identify more genetic correlates of WHS traits, as well as to further characterize the mechanism of seizures based on this study’s findings. Such studies aim to identify potential treatments for many of the medical issues faced by individuals with WHS. (By Dr. Karen Ho, Dr. John Carey, and Dr. Agatino Battaglia, )


Identification of novel genetic causes of Rett syndrome-like phenotypes

6 Jan, 16 | by hqqu

Rett syndrome (RTT) is a severe neurodevelopmental disorder. We investigated a group of 19 MECP2 and CDKL5 negative RTT-like patients. Pathogenic genomic imbalances were found in two patients: a 18q21.2 deletion encompassing TCF4 and a mosaic uniparental disomy of chromosome 3. Very likely pathogenic sequence variants were identified through exome sequencing in genes previously implicated in neurodevelopmental disorders (EEF1A2, STXBP1, ZNF238, SLC35A2, ZFX, SHROOM4 and EIF2B2) as well as in novel candidate genes (RHOBTB2, SMARCA1, GABBR2, EIF4G1 and HTT), potentially explaining disease in 68% of the cases. Bioinformatics analysis shows significant interaction between the novel and previously known RTT-causative genes. (By Fátima Lopes, )

Lopes F Barbosa M et al_2015_Figure 1

Current needs for human and medical genomics research infrastructure in low and middle income countries

6 Jan, 16 | by hqqu

Researchers from Colombia, China, India, Mexico, South Africa, Australia, United States and Canada address “Current Needs for Human and Medical Genomics Research Infrastructure in Low and Middle Income Countries”. Due to the high costs of the needed research infrastructure, a large number of the human genomic centers around the globe are located in developed countries. The authors review successful examples of existing genomics centers in Low and Middle Income Countries (LMIC) and suggest valuable recommendations to develop the research infrastructure that is needed in these LMIC to carry out medical genomics research. (By Dr. Diego A. Forero, )


KCNT1 mutations in seizure disorders: the phenotypic spectrum and functional effects

6 Jan, 16 | by hqqu

Mutations in the potassium channel subunit gene KCNT1 have been identified during the past three years in patients with neurological disorders including nocturnal frontal lobe epilepsy, epileptic encephalopathies and white matter diseases. KCNT1 mutations have also been linked to cardiac arrhythmias. In this review we describe the current knowledge of the KCNT1 gene and its protein product. We discuss the mutational spectrum and range of disorders associated with KCNT1, KCNT1 protein function, the functional effect of KCNT1 mutations, and how this may be related to disease causation. We also discuss preliminary clinical trials of the drug quinidine as a treatment for patients with KCNT1-related disorders. Quinidine alters KCNT1 channel function and its potential use in the treatment of these disorders is an example of personalised medicine based on genetic information. (By Dr. Sarah Heron, )

Gene editing of DNAH11 restores normal cilia motility in primary ciliary dyskinesia

5 Jan, 16 | by hqqu

Primary ciliary dyskinesia (PCD) is a genetic disorder that severely affects the quality of life, manifests early in life, and leads to premature death. PCD is characterized by dysfunction of motile cilia that causes progressive impairment of pulmonary function and severe respiratory infections. There is no specific cure.

This study demonstrates that gene dysfunction causing PCD can be permanently eliminated. This result has been achieved by replacing the mutated with the normal sequence into defective cells. The approach used, also known as gene editing, is easily transferable to other genes affecting ciliary motility of the respiratory epithelia and opens new avenues to cure PCD, cystic fibrosis, and other genetic diseases of the respiratory tract. (By Prof. Mauro Pistello, )

Video: Cilia at the cytoplasmic membrane are beating after the genetic defect has been repair.

JMG blog homepage

JMG Contact

Research developments and evidence-based medical genetics. Visit site

Creative Comms logo

Latest from Journal of Medical Genetics

Latest from Journal of Medical Genetics