The challenges of genetically diagnosing complex I deficiency, the most common cause of childhood-onset mitochondrial disease, are not only due to the very broad spectrum of clinical presentations, but also because of the large number of potential disease-causing genes. This review discusses the structure and function of complex I in light of recent X-ray crystallographic […]
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Recessive germline SDHA and SDHB mutations causing leukodystrophy and isolated mitochondrial complex II deficiency
Mitochondrial diseases affect both children and adults and are clinically and genetically diverse, on account of the dual genetic control of mitochondrial function. Isolated complex II deficiency is a rare form of mitochondrial disease, due to autosomal recessive mutations in either structural components of this enzyme (the SDHA, SDHB, SDHC and SDHD genes) or two […]
Exome sequencing identifies a COL14A1 mutation in a large Chinese pedigree with punctate palmoplantar keratoderma
Punctate palmoplantar keratoderma (PPPK) is a rare autosomal dominant skin disorder characterized by numerous hyperkeratotic papules irregularly distributed on the palms and soles. To date, no causal gene for this disease has been identified. The authors identified a novel heterozygous mutation (c.4505C->T [p.Pro1502Leu]) in COL14A1 gene using exome sequencing, which is a missense substitution at […]
Dominantly inherited diabetes mellitus caused by GATA6 haploinsufficiency: variable intrafamilial presentation
So far, abnormality of the GATA6 gene has been linked to only two clinical conditions: congenital heart malformation and recently described pancreatic agenesis. Previously reported cases of GATA6 pancreatic disease were sporadic and born with a total or near-total absence of the pancreas, most of them accompanied by severe neonatal diabetes mellitus and heart malformation. […]
Quantitative trait locus analysis for next-generation sequencing with the functional linear models
It is now well documented that next-generation sequencing (NGS) can generate several millions or even dozens of millions of genetic variation data. As a consequence, these genetic variation data are so densely distributed across the genome that the genetic variation can be modeled as a function of genomic location. But, standard multivariate statistical analysis often […]
Neurofibromatosis type 1: from genotype to phenotype
Although neurofibromatosis 1 (NF1) is a common genetic disorder, its expression is highly variable and unpredictable. Here, we review the genotype-phenotype correlations in NF1. Some NF1 patients with a given NF1 mutation may develop very severe disease while others with the same mutation have only mild symptoms, even in the same family. The clinical variability […]
A systematic review of associated structural and chromosomal defects in oral clefts: when is prenatal genetic analysis indicated?
Oral clefts are being diagnosed prenatally more frequently. When informing future parents on outcome and prognosis, the category of cleft as well as the presence of other structural congenital anomalies is crucial. Especially the identification of an underlying chromosomal defect will influence prenatal counselling and management of the pregnancy significantly. To provide a basis for […]
Clinical significance of copy number variations in the 11p15.5 imprinting control regions: new cases and review of the literature
The chromosomal region 11p15 harbours several imprinted genes, i.e. genes which are expressed in a parent-of-origin manner. Opposite molecular disturbances in 11p15 are associated with two distinct disorders associated with disturbed growth, Silver-Russell and Beckwith-Wiedemann syndrome. Due to the complexity of the 11p15 region and the interactions between the different genes, the interpretation of copy […]
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Identification of the first recurrent PAR1 deletion in Léri-Weill dyschondrosteosis and idiopathic short stature reveals the presence of a novel SHOX enhancer
SHOX, is a gene implicated in human growth. Defects in SHOX, or its regulatory regions have been observed in ~60% of Léri-Weill dyschondrosteosis (LWD) patients, a skeletal dysplasia, and in 2-5% of idiopathic short stature (ISS) patients. In this study, we identified the first recurrent deletion within the SHOX regulatory region in these disorders, 19/124 […]