Seipin is a protein encoded by BSCL2 gene. BSCL2 mutations can produce congenital generalized lipodystrophy (Berardinelli-Seip syndrome). We have discovered that a novel BSCL2 mutation, c.985C>T, is responsible of a new severe degenerative brain disease, leading to death before age 9. This mutation causes an alternative splicing site leading to the skipping of BSCL2 exon 7, which produces an aberrant seipin.

Strikingly, homozygous children did not show lipodystrophy, whereas compound heterozygous shown a mixed phenotype, lipodystrophy plus neurodegeneration. Patients showed a severe loss of neurons affecting cerebral cortex and basal ganglia. Moreover, we have found that aberrant seipin appeared, beside in endoplasmic reticulum, also in the nucleus of transfected HeLa cells. (By Dr. David Araujo-Vilar, jmedgenet-2013-101525). (By Dr. David Araujo-Vilar, http://jmg.bmj.com/content/early/2013/04/05/jmedgenet-2013-101525 )

There are few empirical data to inform the use and regulation of direct-to-consumer (DTC) genome-wide disease risk tests. The Scripps Genomic Health Initiative is a prospective longitudinal cohort study that aims to determine the psychological, behavioral, and clinical impacts of genomic testing for common disease susceptibility.  Our findings at one-year follow-up indicate that over a third of 2240 DTC genomic test recipients shared their results with their physician, and that this sharing was associated with higher rates of health screening test completion. Genomic testing was not associated with psychological risks, and most participants perceived the test to be of high personal utility. (By Dr. Cinnamon Bloss, http://jmg.bmj.com/content/early/2013/04/03/jmedgenet-2012-101207 )

We performed a genome-wide association study to identify genetic variants that confer susceptibility to chronic kidney disease (CKD) in Japanese. The rs9846911 at 3q28 was significantly associated with CKD in Japanese. The rs2074381 and rs2074380 of ALPK1 at 4q25 were also significantly associated with CKD in individuals with diabetes mellitus. Combined genotype analysis of these three SNPs revealed that the largest odds ratio for the high-risk genotype was 4.2 compared with the low-risk genotype. Chromosome 3q28 may be a susceptibility locus for CKD in Japanese, and ALPK1 may be a susceptibility gene for CKD in such individuals with diabetes mellitus. (By Dr. Yoshiji Yamada, http://jmg.bmj.com/content/early/2013/03/27/jmedgenet-2013-101518 )

Families with mutations in BRCA1/BRCA2 genes have a high-risk of both breast and ovarian cancer.  We examined whether there was increased ovarian cancer risk in families which were untested or tested negative for BRCA1/2 mutations.  By performing person-years at risk analyses on 8005 women from 895 families we found there to be no increased risk of ovarian cancer in families that tested negative for BRCA1 /BRCA2, or were untested, compared to the general population.  Our findings can help with counselling women from BRCA1/2 negative families with breast cancer that their risk of invasive ovarian cancer is not higher than the general population. (By Dr. Sarah Ingham, http://jmg.bmj.com/content/early/2013/03/27/jmedgenet-2013-101607 )

Sarcoidosis is a systemic granulomatous disorder most commonly affecting the lung. While we do not know its cause/s, there is compelling evidence that a genetic predisposition to developing the disease exists. However, sarcoidosis is not a single-gene disorder; instead, it is likely to result from a complex interplay of multiple genes and environmental factors. The host genetic profile is also likely to account for the wide variety of observed clinical manifestations, outcomes, and response to treatment.

The aim of this review is to discuss recent advances in genetics of sarcoidosis – with emphasis on recently performed genome-wide association studies – as well as practical issues and implications for both patients and physicians of such progress. (By Dr. Paolo Spagnolo, http://jmg.bmj.com/content/early/2013/03/21/jmedgenet-2013-101532 )

The Mexican population has an increased susceptibility to dyslipidemias predisposing to coronary heart disease. We performed the first Mexican GWAS for lipids in which we observed a novel locus for high triglycerides near the NPC1 gene. Using cross-ethnic mapping we also restricted several GWAS loci shared between Mexicans and Europeans. At the APOA5 locus, we demonstrate a direct link between the TG-associated variant and postprandial serum apoAV protein levels. Furthermore, our study provides the first comprehensive search for establishing which European loci can be generalized to Mexicans, and demonstrates thus the importance of utilizing diverse populations in genomic lipid studies. (By Dr. Daphna Weissglas-Volkov, http://jmg.bmj.com/content/early/2013/03/14/jmedgenet-2012-101461 )

Remarkable advances in our understanding of epilepsies have occurred over the last 15 years. Concepts about etiology of epilepsies have been transformed from largely unknown to predominantly genetic through clinical genetic and molecular genetic advances. In this review we contrast the early breakthroughs in epilepsy genetics including the contribution of susceptibility alleles, de novo mutations and copy number variants using traditional genetic approaches with the rapid gene discovery now possible using new sequencing technologies. The successful rise of this latter technology provides the first real opportunity to unravel the complex genetic epilepsies and allow widespread clinical application of the discoveries. (By Drs. Sam Berkovic and Michael Hildebrand, http://jmg.bmj.com/content/early/2013/03/05/jmedgenet-2012-101448 )

Congenital nephrotic syndrome is a rare kidney disease in which affected infants lose protein in the urine and eventually develop kidney failure.  Most cases are due to mutations in one of five genes.  We have identified a mutation in a new gene, ARHGDIA, encoding Rho GDP dissociation inhibitor alpha (RhoGDIa) that is responsible for this disorder in two sisters. RhoGDIa interacts with a family of proteins called the Rho-family of small GTPases that regulate the structure and motility of cells.  Our data demonstrates that the mutation in ARHGDIA disrupts the function of cells within the kidney that normally prevent the loss of protein.  (By Dr. Indra Gupta, http://jmg.bmj.com/content/early/2013/02/21/jmedgenet-2012-101442 )

Congenital multiple intestinal atresia is a fatal disorder affecting newborn infants, with the occurrence of numerous obstructions in the small and large intestines, sometimes associated with severe immune deficiency. A genetic origin for the disease was suspected but until now no specific gene had been identified. By performing genome-wide sequencing of DNA from five affected children we found mutations in the gene TTC7A that are likely to cause the disease.  Previously little was known about this gene: now, by further studying the gene’s function we hope to gain a deeper understanding of the biology of this devastating disease. (By Dr. Bruno Maranda, http://jmg.bmj.com/content/early/2013/02/18/jmedgenet-2012-101483 )

Our patients had epilepsy onset in infancy as part of a severe disease affecting the brain that led to death in childhood. We found the underlying mutation. Previously two epilepsy families were described with defects in the same gene. The Italian patients had normal neurological and mental development whereas the Arab patients had moderate intellectual disability. Except for the same form of epilepsy that began in infancy, the diseases in the three families seemed different, likely due to different mutation severity, in spite of the fact that the mutation in our patients does not affect two of the three proteins encoded by the gene whereas the other mutations affect all. (By Dr. Asli Tolun, http://jmg.bmj.com/content/50/3/199 )