Bi-allelic TTC5 variants cause delayed developmental milestones and intellectual disability
J Med Genet. 2021 Apr;58(4):237-246. doi: 10.1136/jmedgenet-2020-106849. Epub 2020 May 21. ABSTRACT BACKGROUND: Intellectual disability syndromes (IDSs) with or without developmental delays affect up to 3% of the world population. We sought to clinically and genetically characterise a novel IDS segregating in five unrelated consanguineous families. METHODS: Clinical analyses were performed for eight patients with […]
Closing in on Mechanisms of Open Neural Tube Defects
Trends Neurosci. 2020 Jul;43(7):519-532. doi: 10.1016/j.tins.2020.04.009. Epub 2020 May 15. ABSTRACT Neural tube defects (NTDs) represent a failure of the neural plate to complete the developmental transition to a neural tube. NTDs are the most common birth anomaly of the CNS. Following mandatory folic acid fortification of dietary grains, a dramatic reduction in the incidence […]
Molecular diagnosis in recessive pediatric neurogenetic disease can help reduce disease recurrence in families
BMC Med Genomics. 2020 May 13;13(1):68. doi: 10.1186/s12920-020-0714-1. ABSTRACT BACKGROUND: The causes for thousands of individually rare recessive diseases have been discovered since the adoption of next generation sequencing (NGS). Following the molecular diagnosis in older children in a family, parents could use this information to opt for fetal genotyping in subsequent pregnancies, which could […]
Second Tier Molecular Genetic Testing in Newborn Screening for Pompe Disease: Landscape and Challenges
Int J Neonatal Screen. 2020 Jun;6(2):32. doi: 10.3390/ijns6020032. Epub 2020 Apr 5. ABSTRACT Pompe disease (PD) is screened by a two tier newborn screening (NBS) algorithm, the first tier of which is an enzymatic assay performed on newborn dried blood spots (DBS). As first tier enzymatic screening tests have false positive results, an immediate second […]
Novel congenital disorder of O-linked glycosylation caused by GALNT2 loss of function
Brain. 2020 Apr 1;143(4):1114-1126. doi: 10.1093/brain/awaa063. ABSTRACT Congenital disorders of glycosylation are a growing group of rare genetic disorders caused by deficient protein and lipid glycosylation. Here, we report the clinical, biochemical, and molecular features of seven patients from four families with GALNT2-congenital disorder of glycosylation (GALNT2-CDG), an O-linked glycosylation disorder. GALNT2 encodes the Golgi-localized […]
RSRC1 loss-of-function variants cause mild to moderate autosomal recessive intellectual disability
Brain. 2020 Apr 1;143(4):e31. doi: 10.1093/brain/awaa070. NO ABSTRACT PMID:32227164 | PMC:PMC7174030 | DOI:10.1093/brain/awaa070
Bi-allelic Variants in the GPI Transamidase Subunit PIGK Cause a Neurodevelopmental Syndrome with Hypotonia, Cerebellar Atrophy, and Epilepsy
Am J Hum Genet. 2020 Apr 2;106(4):484-495. doi: 10.1016/j.ajhg.2020.03.001. Epub 2020 Mar 26. ABSTRACT Glycosylphosphatidylinositol (GPI)-anchored proteins are critical for embryogenesis, neurogenesis, and cell signaling. Variants in several genes participating in GPI biosynthesis and processing lead to decreased cell surface presence of GPI-anchored proteins (GPI-APs) and cause inherited GPI deficiency disorders (IGDs). In this report, […]
Pathogenic variants in SQOR encoding sulfide:quinone oxidoreductase are a potentially treatable cause of Leigh disease
J Inherit Metab Dis. 2020 Sep;43(5):1024-1036. doi: 10.1002/jimd.12232. Epub 2020 Apr 15. ABSTRACT Hydrogen sulfide, a signaling molecule formed mainly from cysteine, is catabolized by sulfide:quinone oxidoreductase (gene SQOR). Toxic hydrogen sulfide exposure inhibits complex IV. We describe children of two families with pathogenic variants in SQOR. Exome sequencing identified variants; SQOR enzyme activity was […]
Maternal Hypertension-Related Genotypes and Congenital Heart Defects
Am J Hypertens. 2021 Feb 18;34(1):82-91. doi: 10.1093/ajh/hpaa116. ABSTRACT BACKGROUND: Maternal hypertension has been associated with congenital heart defect occurrence in several studies. We assessed whether maternal genotypes associated with this condition were also associated with congenital heart defect occurrence. METHODS: We used data from the National Birth Defects Prevention Study to identify non-Hispanic white […]
Determining the incidence of rare diseases
Hum Genet. 2020 May;139(5):569-574. doi: 10.1007/s00439-020-02135-5. Epub 2020 Feb 13. ABSTRACT Extremely rare diseases are increasingly recognized due to wide-spread, inexpensive genomic sequencing. Understanding the incidence of rare disease is important for appreciating its health impact and allocating recourses for research. However, estimating incidence of rare disease is challenging because the individual contributory alleles are, […]