Improved attention linked to sustained phenylalanine reduction in adults with early-treated phenylketonuria
Am J Med Genet A. 2021 Nov 26. doi: 10.1002/ajmg.a.62574. Online ahead of print. ABSTRACT Pegvaliase is approved to reduce phenylalanine (Phe) levels for people with phenylketonuria (PKU). PRISM-1 (NCT01819727) and PRISM-2 (NCT01889862) data were analyzed to evaluate the relationship between Phe and inattention in adult participants with PKU. In the modified-intent-to-treat population (N = […]
Biallelic FRA10AC1 variants cause a neurodevelopmental disorder with growth retardation
Brain. 2021 Oct 25:awab403. doi: 10.1093/brain/awab403. Online ahead of print. ABSTRACT The major spliceosome mediates pre-mRNA splicing by recognizing the highly conserved sequences at the 5′ and 3′ splice sites and the branch point. More than 150 proteins participate in the splicing process and are organized in the spliceosomal A, B, and C complexes. FRA10AC1 […]
Development of therapies for rare genetic disorders of GPX4: roadmap and opportunities
Orphanet J Rare Dis. 2021 Oct 23;16(1):446. doi: 10.1186/s13023-021-02048-0. ABSTRACT BACKGROUND: Extremely rare progressive diseases like Sedaghatian-type Spondylometaphyseal Dysplasia (SSMD) can be neonatally lethal and therefore go undiagnosed or are difficult to treat. Recent sequencing efforts have linked this disease to mutations in GPX4, with consequences in the resulting enzyme, glutathione peroxidase 4. This offers […]
Expanding the phenotypic spectrum of BCS1L-related mitochondrial disease
Ann Clin Transl Neurol. 2021 Oct 18. doi: 10.1002/acn3.51470. Online ahead of print. ABSTRACT OBJECTIVE: To delineate the full phenotypic spectrum of BCS1L-related disease, provide better understanding of the genotype-phenotype correlations and identify reliable prognostic disease markers. METHODS: We performed a retrospective multinational cohort study of previously unpublished patients followed in 15 centres from 10 […]
Artificial intelligence enables comprehensive genome interpretation and nomination of candidate diagnoses for rare genetic diseases
Genome Med. 2021 Oct 14;13(1):153. doi: 10.1186/s13073-021-00965-0. ABSTRACT BACKGROUND: Clinical interpretation of genetic variants in the context of the patient’s phenotype is becoming the largest component of cost and time expenditure for genome-based diagnosis of rare genetic diseases. Artificial intelligence (AI) holds promise to greatly simplify and speed genome interpretation by integrating predictive methods with […]
Caenorhabditis elegans provides an efficient drug screening platform for GNAO1-related disorders and highlights the potential role of caffeine in controlling dyskinesia
Hum Mol Genet. 2021 Oct 8:ddab296. doi: 10.1093/hmg/ddab296. Online ahead of print. ABSTRACT Dominant GNAO1 mutations cause an emerging group of childhood-onset neurological disorders characterized by developmental delay, intellectual disability, movement disorders, drug-resistant seizures, and neurological deterioration. GNAO1 encodes the α-subunit of an inhibitory GTP/GDP-binding protein regulating ion channel activity and neurotransmitter release. The pathogenic […]
YY1: A New Gene for Childhood Onset Dystonia with Prominent Oromandibular-Laryngeal Involvement?
Mov Disord. 2021 Oct 7. doi: 10.1002/mds.28813. Online ahead of print. NO ABSTRACT PMID:34618373 | DOI:10.1002/mds.28813
Dual orexin receptor antagonists for insomnia in youth with neurodevelopmental disorders: a case series and review
Eur Child Adolesc Psychiatry. 2021 Oct 5. doi: 10.1007/s00787-021-01883-7. Online ahead of print. ABSTRACT Insomnia is a common, impairing, and difficult-to-treat comorbidity in children with neurodevelopmental disorders (NDDs). Behavioral interventions can be challenging because of developmental and behavioral features that interfere with treatment. Medication management also can be difficult due to a high burden of […]
Biallelic variants in SLC38A3 encoding a glutamine transporter cause epileptic encephalopathy
Brain. 2021 Oct 4:awab369. doi: 10.1093/brain/awab369. Online ahead of print. ABSTRACT The solute carrier (SLC) superfamily encompasses >400 transmembrane transporters involved in the exchange of amino acids, nutrients, ions, metals, neurotransmitters and metabolites across biological membranes. SLCs are highly expressed in the mammalian brain; defects in nearly 100 unique SLC-encoding genes (OMIM: https://www.omim.org) are associated […]
ABHD16A deficiency causes a complicated form of hereditary spastic paraplegia associated with intellectual disability and cerebral anomalies
Am J Hum Genet. 2021 Sep 21:S0002-9297(21)00341-4. doi: 10.1016/j.ajhg.2021.09.005. Online ahead of print. ABSTRACT ABHD16A (abhydrolase domain-containing protein 16A, phospholipase) encodes the major phosphatidylserine (PS) lipase in the brain. PS lipase synthesizes lysophosphatidylserine, an important signaling lipid that functions in the mammalian central nervous system. ABHD16A has not yet been associated with a human disease. […]