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Article
Exome sequencing in four families with neurodevelopmental disorders: genotype–phenotype correlation and identification of novel disease-causing variants in VPS13B and RELN
Neurodevelopmental disorders (NDDs) are a clinically and genetically heterogeneous group of early-onset pediatric disorders that affect the structure and/or function of the central or peripheral nervous system...
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Article
Open AccessPathogenic variants in SLF2 and SMC5 cause segmented chromosomes and mosaic variegated hyperploidy
Embryonic development is dictated by tight regulation of DNA replication, cell division and differentiation. Mutations in DNA repair and replication genes disrupt this equilibrium, giving rise to neurodevelopm...
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Article
Testing for rare genetic causes of obesity: findings and experiences from a pediatric weight management program
Genetic screening for youth with obesity in the absence of syndromic findings has not been part of obesity management. For children with early onset obesity, genetic screening is recommended for those having c...
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Article
A recessive variant in TFAM causes mtDNA depletion associated with primary ovarian insufficiency, seizures, intellectual disability and hearing loss
Mitochondrial disorders are collectively common, genetically heterogeneous disorders in both pediatric and adult populations. They are caused by molecular defects in oxidative phosphorylation, failure of essen...
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Article
Open AccessAcoustofluidic rotational tweezing enables high-speed contactless morphological phenoty** of zebrafish larvae
Modern biomedical research and preclinical pharmaceutical development rely heavily on the phenoty** of small vertebrate models for various diseases prior to human testing. In this article, we demonstrate an ...
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Article
Open AccessCFAP45 deficiency causes situs abnormalities and asthenospermia by disrupting an axonemal adenine nucleotide homeostasis module
Axonemal dynein ATPases direct ciliary and flagellar beating via adenosine triphosphate (ATP) hydrolysis. The modulatory effect of adenosine monophosphate (AMP) and adenosine diphosphate (ADP) on flagellar bea...
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Article
Evidence for secondary-variant genetic burden and non-random distribution across biological modules in a recessive ciliopathy
The influence of genetic background on driver mutations is well established; however, the mechanisms by which the background interacts with Mendelian loci remain unclear. We performed a systematic secondary-va...
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Article
Open AccessMutations in FAM50A suggest that Armfield XLID syndrome is a spliceosomopathy
Intellectual disability (ID) is a heterogeneous clinical entity and includes an excess of males who harbor variants on the X-chromosome (XLID). We report rare FAM50A missense variants in the original Armfield XLI...
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Article
Open AccessSmall molecule inhibition of RAS/MAPK signaling ameliorates developmental pathologies of Kabuki Syndrome
Kabuki Syndrome (KS) is a rare disorder characterized by distinctive facial features, short stature, skeletal abnormalities, and neurodevelopmental deficits. Previously, we showed that loss of function of RAP1...
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Article
Open AccessZebrafish knockout of Down syndrome gene, DYRK1A, shows social impairments relevant to autism
DYRK1A maps to the Down syndrome critical region at 21q22. Mutations in this kinase-encoding gene have been reported to cause microcephaly associated with either intellectual disabilit...
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Article
Open AccessPartial uniparental isodisomy of chromosome 16 unmasks a deleterious biallelic mutation in IFT140 that causes Mainzer-Saldino syndrome
The ciliopathies represent an umbrella group of >50 clinical entities that share both clinical features and molecular etiology underscored by structural and functional defects of the primary cilium. Despite th...
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Article
Correction: Corrigendum: SMCHD1 mutations associated with a rare muscular dystrophy can also cause isolated arhinia and Bosma arhinia microphthalmia syndrome
Nat. Genet. 49, 238–248 (2017); published online 9 January 2017; corrected after print 20 March 2017 In the version of this article initially published, the legend to Figure 4c stated that only one proband wit...
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Article
SMCHD1 mutations associated with a rare muscular dystrophy can also cause isolated arhinia and Bosma arhinia microphthalmia syndrome
Michael Talkowski, David FitzPatrick, Erica Davis and colleagues report rare inherited or de novo missense variants in SMCHD1 in arhinia patients. Some of the same mutations in SMCHD1 are known to cause a phenoty...
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Article
Open AccessAn organelle-specific protein landscape identifies novel diseases and molecular mechanisms
Cellular organelles provide opportunities to relate biological mechanisms to disease. Here we use affinity proteomics, genetics and cell biology to interrogate cilia: poorly understood organelles, where defect...
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Article
Identification of cis-suppression of human disease mutations by comparative genomics
Patterns of amino acid conservation have been used to guide the interpretation of the disease-causing potential of genetic variants in patients; now, an appreciable fraction of pathogenic alleles are shown to ...
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Article
Open AccessRapid and Efficient Generation of Transgene-Free iPSC from a Small Volume of Cryopreserved Blood
Human peripheral blood and umbilical cord blood represent attractive sources of cells for reprogramming to induced pluripotent stem cells (iPSCs). However, to date, most of the blood-derived iPSCs were generat...
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Article
Gene therapy rescues cilia defects and restores olfactory function in a mammalian ciliopathy model
Ciliopathies are caused by alterations in the development and function of cilia. Now Jeffrey Martens and his colleagues demonstrate anatomic and functional rescue of cilia development in mature, differentiated...
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Article
KIF7 mutations cause fetal hydrolethalus and acrocallosal syndromes
Tania Attié-Bitach and colleagues report that biallelic mutations in KIF7, a component of the Hedgehog signaling pathway, cause hydrolethalus and acrocallosal syndromes. They also present evidence that heterozygo...
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Article
Correction: Corrigendum: TTC21B contributes both causal and modifying alleles across the ciliopathy spectrum
Nat. Genet. 43, 189–196 (2011); published online 23 January 2011; corrected after print 29 March 2011 In the version of this article initially published, the authors should have acknowledged that the work was ...
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Article
TTC21B contributes both causal and modifying alleles across the ciliopathy spectrum
Nicholas Katsanis and colleagues show that biallelic mutations in TTC21B, encoding the retrograde intraflagellar transport protein IFT139, are associated with diverse ciliopathy phenotypes in humans. They further...
