Posts By: Alina Levtova

Defects of the mitochondrial S-adenosylmethionine transporter cause intramitochondrial methylation deficiency

Posted by & filed under Part 10: DISORDERS OF MITOCHONDRIAL FUNCTION, _.

Mutations in SLC25A26, encoding the mitochondrial S-adenosylmethionine (SAM) transporter, were identified in patients in three families though homozygosity mapping and exome sequencing. Clinical manifestations ranged from foetal hydrops to episodes of lactic acidosis and cardiopulmonary collapse in childhood with chronic progressive muscle weakness. The authors showed that the defect of SAM import into mitochondria causes […]

Biotinidase deficiency should be considered in the differential diagnosis of myelopathy

Posted by & filed under Part 17: VITAMINS, _.

In this review, B. Wolf highlights the importance of considering biotinidase deficiency in the differential diagnosis of myelopathy. He reviews 18 previously reported patients who presented with spastic para- or tetraplegia due to myelopathy with and without vision loss and were ultimately diagnosed with profound biotinidase deficiency, but often after a prolonged diagnostic odyssey resulting […]

New phenotype associated with phosphoribosyl pyrophosphate synthetase 1 deficiency

Posted by & filed under Exome sequencing, Part 11: PURINES AND PYRIMIDINES.

Al-Maawali A et al. Prenatal growth restriction, retinal dystrophy, diabetes insipidus and white matter disease: expanding the spectrum of PRPS1-related disorders. European Journal of Human Genetics (2015) 23, 310–316.   Phosphoribosyl pyrophosphate synthetase 1 (PRS-1) catalyses the first step of purine synthesis, and several X-linked disorders have been associated with both its deficiency (Arts syndrome, […]

A2ML1 mutations are associated with a Noonan-like syndrome

Posted by & filed under Exome sequencing, Part 30: MULTISYSTEM INBORN ERRORS OF DEVELOPMENT.

Vissers L et al. Heterozygous germline mutations in A2ML1 are associated with a disorder clinically related to Noonan syndrome. European Journal of Human Genetics (2015) 23, 317-324.   For a quarter of patients clinically diagnosed with Noonan syndrome, the molecular cause cannot be identified. Through exome sequencing in a case-parent trio, followed by targeted resequencing […]

Genome-wide association study of MMR-related febrile seizures

Posted by & filed under Part 28: NEUROGENETICS.

Feenstra B et al. Common variants associated with general and MMR vaccine-related febrile seizures. Nat Genet. 2014 Dec;46(12):1274-82. Epub 2014 Oct 26. Febrile seizures are a well-known side-effect of MMR (measles-mumps-rubella) vaccination. Polymorphisms associated with an increased risk of febrile seizures in general have been identified previously (particularly in genes encoding ion channels); this study […]

Folinic acid in the treatment of schizophrenia associated with folate receptor antibodies

Posted by & filed under Part 17: VITAMINS.

Ramaekers VT et al. Folinic acid treatment for schizophrenia associated with folate receptor autoantibodies. Mol Genet Metab. 2014 Dec;113(4):307-14.   This study suggests an exciting avenue for treatment and scientific inquiry  in schizophrenia. Previous reports have associated schizophrenia with perturbed folate metabolism, and cerebral folate deficiency due to serum antibodies against folate receptor alpha (which transfers […]

Thiamine pyrophosphokinase deficiency: a treatable inborn error of metabolism

Posted by & filed under Part 17: VITAMINS.

Banka S et al. Expanding the clinical and molecular spectrum of thiamine pyrophosphokinase deficiency: A treatable neurological disorder caused by TPK1 mutations. Mol Genet Metab. 2014 Oct 5. [Epub ahead of print]   Thiamine pyrophosphokinase (TPK) deficiency causing episodic encephalopathy type thiamine metabolism dysfunction is the most recently discovered thiamine-responsive inborn error of metabolism, with […]

Towards chaperone therapy in pyridoxine-resistant classical homocystinuria

Posted by & filed under Part 08: AMINO ACIDS.

Melenovská P, Kopecká J, Krijt J, Hnízda A, Raková K, Janošík M, Wilcken B, Kožich V.  Chaperone therapy for homocystinuria: the rescue of CBS mutations by heme arginate. J Inherit Metab Dis. 2014 Oct 21. [Epub ahead of print]   Mutations in the CBS gene cause classical homocystinuria (cystathionine beta-synthase deficiency). For patients who do not […]

A framework for the interpretation of de novo mutation in human disease

Posted by & filed under Exome sequencing, Part 28: NEUROGENETICS.

Samocha et al. A framework for the interpretation of de novo mutation in human disease. Nat Genet. 2014 Aug 3.   Samocha et al describe a sophisticated statistical model designed to better evaluate data derived from mass exome sequencing studies, specifically with respect to the significance of excesses of de novo mutations in diseases with […]

HMGCR is a genetic modifier for risk, age of onset and MCI conversion to Alzheimer’s disease

Posted by & filed under Part 12: LIPIDS, Part 28: NEUROGENETICS.

Leduc V et al. HMGCR is a genetic modifier for risk, age of onset and MCI conversion to Alzheimer’s disease in a three cohorts study. Mol Psychiatry. 2014 Jul 15 Leduc et al report a new genetic modulator of the risk for sporadic Alzheimer’s disease (AD) occurrence, as well as the risk of conversion from […]