Case report: A novel biallelic variant causing multisystem anomalies with severe epilepsy, widening the spectrum of syndrome.

The fat mass and obesity-associated gene () codes for a DNA/RNA demethylase. Pathological variants in this gene are rare, with only three reports in the literature, all with mutations in the catalytic domain. We report the first biallelic human variant in fat mass and obesity-associated gene (c.

Exome sequencing of 20,979 individuals with epilepsy reveals shared and distinct ultra-rare genetic risk across disorder subtypes.

Identifying genetic risk factors for highly heterogeneous disorders like epilepsy remains challenging. Here, we present the largest whole-exome sequencing study of epilepsy to date, with >54,000 human exomes, comprising 20,979 deeply phenotyped patients from multiple genetic ancestry groups with diverse epilepsy subtypes and 33,444 controls, to investigate rare variants that confer disease risk. These analyses implicate seven individual genes, three gene sets, and four copy number variants at exome-wide significance.

Diagnosis and Supportive Management of Fucosidosis: A Case Report.

Fucosidosis is a lysosomal storage disease, resulting from a deficiency of the enzyme alpha-L-fucosidase. We present the case of an affected female with numerous manifestations, clinically and radiographically. In fucosidosis, advanced interventions are not always necessary to have rewarding outcomes.

Epilepsy surgery in patients with autism.

OBJECTIVE The purpose of this study was to report outcomes of epilepsy surgery in 56 consecutive patients with autism spectrum disorder. METHODS Medical records of 56 consecutive patients with autism who underwent epilepsy surgery were reviewed with regard to clinical characteristics, surgical management, postoperative seizure control, and behavioral changes. RESULTS Of the 56 patients with autism, 39 were male, 45 were severely autistic, 27 had a history of clinically significant levels of aggression and other disruptive behaviors, and 30 were considered nonverbal at baseline.

CEP41 is mutated in Joubert syndrome and is required for tubulin glutamylation at the cilium.

Tubulin glutamylation is a post-translational modification that occurs predominantly in the ciliary axoneme and has been suggested to be important for ciliary function. However, its relationship to disorders of the primary cilium, termed ciliopathies, has not been explored. Here we mapped a new locus for Joubert syndrome (JBTS), which we have designated as JBTS15, and identified causative mutations in CEP41, which encodes a 41-kDa centrosomal protein.

Expanding CEP290 mutational spectrum in ciliopathies.

Ciliopathies are an expanding group of rare conditions characterized by multiorgan involvement, that are caused by mutations in genes encoding for proteins of the primary cilium or its apparatus. Among these genes, CEP290 bears an intriguing allelic spectrum, being commonly mutated in Joubert syndrome and related disorders (JSRD), Meckel syndrome (MKS), Senior-Loken syndrome and isolated Leber congenital amaurosis (LCA). Although these conditions are recessively inherited, in a subset of patients only one CEP290 mutation could be detected.

Joubert syndrome: monozygotic twins with discordant phenotypes.

We describe three sisters with Joubert syndrome, two of whom are monozygotic twins with highly discordant phenotypes. The twins were born at 34 weeks' gestation with discordant birthweights. Their anatomic, neurologic, and developmental status differs greatly: Twin B is able to walk, run, and is verbal, unlike Twin A who is wheelchair-bound, severely retarded, nonverbal, and autistic.