Sedaghatian-type spondylometaphyseal dysplasia is a rare syndrome characterized by abnormal bone development with shortened limbs and flattened spine. Affected children also have heart rhythm defects and brain abnormalities such that they pass away shortly after birth. Eighteen infants affected with this rare disease have been reported worldwide. We studied two families and identified loss-of-function mutations […]
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RB1 mutation spectrum in a comprehensive nationwide cohort of retinoblastoma patients (Contributed by Berber Mol)
Retinoblastoma is a cancer of the retina that occurs in young children, in the majority of cases initiated by mutations in the RB1 tumour suppressor gene. About 40% of retinoblastoma patients have a germline RB1 mutation which gives them a hereditary predisposition to develop retinoblastoma. Knowledge of the presence of an RB1 mutation can help […]
Mutation in KANK2, encoding a sequestering protein for steroid receptor coactivators, causes keratoderma and woolly hair (Contributed by Dr. Yuval Ramot)
The combination of keratoderma (thickened palms and soles) with woolly hair should always alert the clinician to the possibility of Naxos or Carvajal syndromes. These two autosomal recessive conditions are caused by mutations in desmosomal proteins, which are critical for cellular adhesion in the skin. Since desmosomes are abundant in the cardiac muscle, these syndromes […]
Genome-wide association study identifies new disease loci for isolated clubfoot (Contributed by Dr. Christina A Gurnett)
Clubfoot is a common congenital birth defect that affects nearly 1 in 1000 births. To identify genetic risk factors associated with clubfoot, we performed a genome-wide association study of 396 isolated clubfoot patients and 1000 controls of European descent. Strongest evidence for an association of clubfoot was found with an intergenic SNP on chromosome 12q24.31 […]
Mapping of hepatic expression quantitative trait loci (eQTLs) in a Han Chinese population (Contributed by Dr. Zhihai Peng)
Understanding genetic control for gene expression in human livers is important to elucidate the mechanism underlying health and disease. Wang et al. carried out the first genome-wide analysis in liver tissues of a Han Chinese population and observed 1,669 genetic loci significantly associated with hepatic gene expression. The study also found that at least 41% […]
CGG allele size somatic mosaicism and methylation in FMR1 premutation alleles (Contributed by Dr. Dalyir I. Pretto)
Premutation alleles within the FMR1 gene are usually unmethylated and have an increased risk of developing a number of clinical phenotypes that fall under the umbrella of FMR1-associated conditions. In this study, we report on a group of premutation carriers who show partial methylation and in some cases we demonstrate the presence of intra and inter-tissue mosaicism. In […]
Prenylation defects in inherited retinal diseases (Contributed by Dr. Anna Siemiatkowska)
To fulfil their specialised functions, retinal proteins are located at specific positions in photoreceptor cells. These cells consist of many different compartments. Proteins are transported between these compartments through their binding to other proteins or to membranous vesicles. To interact with other proteins or vesicles, proteins contain a hydrophobic lipid molecule, a prenyl group. Many […]
Normal and aberrant splicing of LMNA (Contributed by Professor Steve Wilton)
The LMNA gene is ubiquitously expressed and is alternatively spliced to give rise to the nuclear lamina proteins lamin A/C, as well as the truncated product progerin that accumulates in the Hutchinson-Gilford progeria syndrome. Mutations in LMNA can result in a variety of clinical phenotypes, which may involve the skin or skeletal muscles or cause […]
Next generation sequencing of chromosomal rearrangements in patients with split-hand/split-foot malformation provides evidence for DYNC1I1 exonic enhancers of DLX5/6 expression in humans (Contributed by Dr. Hana Lango Allen)
Lango-Allen and colleagues studied two families with split hand/split foot malformation and looked for causal mutations using new genome-wide sequencing technology. In one family they identified a deletion that included specific protein-coding regions of DYNC1I1 gene, recently shown to regulate DLX5/6 genes in the developing mouse and zebrafish limbs. In the second family there was […]
Truncating mutations in TAF4B and ZMYND15 causing recessive azoospermia (Contributed by Professor Aslıhan Tolun)
Approximately 1% of all men do not produce sufficient amount of sperm, and the genetic basis of the majority of cases is unknown. In two unrelated consanguineous families we first found the chromosomal locations of the defective genes responsible for azoospermia and later identified gene defects in TAF4B and ZMYND15. We screened 60 unrelated azoospermic […]