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.


Genome-wide association study identifies variants in HORMAD2 associated with tonsillectomy

9 Dec, 16 | by hqqu

Tonsillectomy is one of the most common surgical procedures in children and young adults and may be recommended in patients who experience recurrent throat infections. Using Danish health register data, we screened the genomes of more than 3,000 tonsillectomy patients and 13,000 controls. Thereby, we identified variants in the gene HORMAD2 significantly associated with tonsillectomy. It is notable that the top associated genetic variant was previously reported to increase the risk of IgA nephropathy, a rare autoimmune disease that affects the kidneys, while it was also reported to decrease the risk of inflammatory bowel disease. Our results underline the complex genetic regulation of the mucosal immune system and its effect on different diseases. (By Dr. Bjarke Feenstra, )



Regional association plot for the tonsillectomy locus on chromosome 22, showing SNP position (x axis) and association with tonsillectomy (-log10 p value; y axis). The top SNP, rs2412971, is represented by a purple diamond, and the other SNPs are colored to reflect their correlation (linkage disequilibrium) with the top SNP. The blue lines show estimated rates of recombination based on data from the HapMap project (right y axis). The names and positions of HORMAD2 and other genes in the region are shown in the lower part of the figure.

A novel somatic mutation achieves partial rescue in a child with Hutchinson-Gilford progeria syndrome

5 Dec, 16 | by hqqu

Progeria is a fatal premature aging disease caused by mutations in the LMNA gene, leading to production of the toxic protein progerin.    We describe a child with a mixed cell population (mosaicism) carrying two different progerin-producing mutations of the same nucleotide – one causing clinically severe Progeria and one milder Progeria.  The child possessed intermediate disease characteristics.  We postulate that the severe mutation represents the original genotype, and the milder variant arose early in embryogenesis and was subjected to positive selection.  This type of mosaicism has not been previously characterized for any disease. Such compensatory mechanisms may occur elsewhere, but go undetected by current genetic screens. (By Dr. Leslie B. Gordon, )

The importance of dynamic re-analysis in diagnostic whole exome sequencing

29 Nov, 16 | by hqqu

Exome sequencing is a method of investigating all of a person¹s genes at the same time to look for the mutation that is causing their illness. It is often used when targeted genetic testing has run into a dead end. However, half to three quarters of patients who have their exome sequenced will still not receive a Œgenetic diagnosis¹. This research by Drs. Anna Need, Vandana Shashi and colleagues explores the reasons that some families do not get a diagnosis through exome sequencing the first time, and presents three patients who received a diagnosis when their exome data was re-analysed.  (By Dr. Anna Need, )

Diagnostic value of exome and whole genome sequencing in craniosynostosis

24 Nov, 16 | by hqqu

Craniosynostosis (the premature fusion of the skull bones) is a common disorder affecting 1 in 2,250 children and so is often encountered by paediatricians and geneticists. Because of the many different genetic causes of this disease, standard diagnostic testing procedures can often miss the underlying genetic lesion. In our study we identified the genetic cause using deep sequencing of the genome in 15 patients from a cohort of 40 (37.5%), and provide specific details of 5 cases where this result has had a direct and immediate impact on the clinical decisions for the child and their families. This study highlights the impact of using these methods to identify the underlying genetic cause in cases that would otherwise have eluded routine clinical testing, in addition to identifying new disease genes to improve diagnostic and management strategies in the future. (By Dr. Kerry Miller, )

Hypersuccinylacetonemia and normal liver function in maleylacetoacetate isomerase deficiency

22 Nov, 16 | by hqqu

Tyrosinemia is a genetic disease that causes liver failure, cirrhosis and liver cancer. Succinylacetone is a substance that is elevated in tyrosinemia. Using succinylacetone for newborn screening permits early treatment of tyrosinemia, which can prevent liver disease. Six babies were detected by screening but had normal liver function. Even without special treatment, each child has maintained normal liver function. Each has a genetic deficiency of an enzyme called maleylacetoacetate isomerase, that is related to but different from the enzyme that causes tyrosinemia. Recognizing this newly-discovered condition is important for proper genetic counselling and treatment of babies detected by tyrosinemia screening. (By Dr. Grant Mitchell, )

Anxiety delivered Direct-to-Consumer: are we asking the right questions about the impacts of DTC genetic testing?

10 Nov, 16 | by hqqu

Contrarily to initial expectations about the psychological impact of Direct to Consumer genetic testing, people are substantially resilient to long-term consequences of results to genetic testing. Previous literature raised concerns on DTC focusing on anxiety levels it might cause. We claim that there are three substantial limits to be considered: non-clinical anxiety is not a negative outcome; anxiety is limitedly predictive of health related behaviors and decisions; a number of previous studies are affected by methodological errors. We promote the exploration of complex cognitive and emotional mechanisms to capture the subtle and multifaceted nature of a living-at-risk situation. (By Dr. Serena Oliveri, )

Oral pharmacological chaperone migalastat compared with enzyme replacement therapy in Fabry disease: 18-month results from the randomised phase III ATTRACT study

10 Nov, 16 | by hqqu

Fabry disease is a rare, inherited disorder due to deficiency of lysosomal α-galactosidase A leading to multisystem disease and early death.

In the 18-month randomized segment of the global ATTRACT study, orally administered migalastat, a first-in-class pharmacological chaperone, was compared with intravenous enzyme replacement therapy. Migalastat and ERT had comparable effects on renal function. Migalastat was associated with a statistically significant decrease in cardiac mass whereas ERT was associated with a smaller non-significant change. Migalastat has potential as an effective and safe oral treatment for 35-50% of patients with Fabry disease who have amenable mutations.  (By Dr. Christopher Viereck, )

The UCL Low-Density Lipoprotein Receptor Gene Variant Database: Pathogenicity Update

7 Nov, 16 | by hqqu

Familial hypercholesterolemia (FH) is a common genetic disorder frequently caused by low-density lipoprotein receptor (LDLR) gene variants.  Patients with FH have high levels of LDL-cholesterol leading to cardiovascular disease including premature heart attacks.  We report an update of the UCL LDLR variant database which is used widely by clinicians and researchers as a catalogue of published variant information and pathogenicity predictions. Over 1700 unique LDLR variants have been reported globally, of which we suggest that 76% are likely to be, or are probably pathogenic, 17% are unlikely to be, or are probably not pathogenic and the remaining 7% are variants of unknown significance, where additional family and in vitro studies will be required to confirm or refute their pathogenicity. (By Dr. Sarah Leigh, )

The cerebellum and embodied semantics: Evidence from a case of genetic ataxia due to STUB1 mutations

3 Nov, 16 | by hqqu

Damage to movement-related brain networks distinctively impairs processing of action verbs (words denoting bodily motion). Can genetically-based deterioration of relevant regions involve similar deficits? To address this question, we assessed lexical processing in a unique patient with cerebellar ataxia due to mutations in the STUB1 gene. By combining structural and functional MRI with genetic and behavioral analysis, we found that such genetic abnormalities are related to selective action-verb impairments, further showing the distinct role of the cerebellum and its connections to semantic- and motor-related cortical regions in processing those words. Our study opens new windows into the role of cerebellar structures and their genetic underpinnings in high-order domains. (By Dr. Agustín Ibáñez, )


Behavioral and imaging results of the patient relative to controls. (A) Behavioral performance.  Lexical decision results indicate a selective deficit for action verbs. AcV: action verbs (p = .03); AbV:  abstract verbs (p = .18); MaN manipulable nouns (p = .23); AbN: abstract nouns (p = .26). (B) Atrophy  pattern. Voxel-based morphometry results revealed a global atrophy pattern markedly involving the left and  right cerebella, in addition to insular, frontal, and temporal regions. (C) Functional connectivity alterations.  Functional connectivity results revealed altered connectivity between peak atrophy site in the cerebellum (x  = -17, y = -60, z = -20) and both temporo-parietal and frontal regions. (D) Gene-atrophy overlap. Overlap  between atrophied areas and sites of expression of the STUB1 gene. Overlap was marked in multiple  cerebellar locations, and also in the fusiform and superior temporal gyri.

AMMECR1: a single point mutation causes developmental delay, midface hypoplasia and elliptocytosis

3 Nov, 16 | by hqqu

Several authors have previously described a syndrome consisting of Alport Syndrome, intellectual disability, midface hypoplasia and elliptocytosis due to a large deletion involving the X chromosome. Previously published cases all had deletions of the X chromosome involving between 6 and 11 genes. We describe two maternal half-brothers who have very similar extra-renal features including midface hypoplasia, intellectual disability and elliptocytosis due to a single base-pair substitution in AMMECR1, a gene within the region of the X chromosome deleted in the previously described cases. Functional studies confirmed that the mutant protein is abnormally distributed within the nucleus of cultured cells. (By Dr. Rodney Gilbert, )

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