Purpose: Protein arginine methyltransferase 7 (PRMT7) is a member of a family of enzymes that catalyzes the methylation of arginine residues on several protein substrates. Biallelic pathogenic... Show morePurpose: Protein arginine methyltransferase 7 (PRMT7) is a member of a family of enzymes that catalyzes the methylation of arginine residues on several protein substrates. Biallelic pathogenic PRMT7 variants have previously been associated with a syndromic neurodevelopmental disorder characterized by short stature, brachydactyly, intellectual developmental disability, and seizures. To our knowledge, no comprehensive study describes the detailed clinical characteristics of this syndrome. Thus, we aim to delineate the phenotypic spectrum of PRMT7-related disorder.Methods: We assembled a cohort of 51 affected individuals from 39 different families, gathering clinical information from 36 newly described affected individuals and reviewing data of 15 individuals from the literature.Results: The main clinical characteristics of the PRMT7-related syndrome are short stature, mild to severe developmental delay/intellectual disability, hypotonia, brachydactyly, and distinct facial morphology, including bifrontal narrowing, prominent supraorbital ridges, sparse eyebrows, short nose with full/broad nasal tip, thin upper lip, full and everted lower lip, and a prominent or squared-off jaw. Additional variable findings include seizures, obesity, nonspecific magnetic resonance imaging abnormalities, eye abnormalities (i.e., strabismus or nystagmus), and hearing loss.Conclusion: This study further delineates and expands the molecular, phenotypic spectrum and natural history of PRMT7-related syndrome characterized by a neurodevelopmental disorder with skeletal, growth, and endocrine abnormalities. (c) 2022 The Authors. Published by Elsevier Inc. on behalf of American College of Medical Genetics and Genomics. Show less
Zhu-Tokita-Takenouchi-Kim (ZTTK) syndrome is caused by de novo loss-of-function variants in the SON gene (MIM #617140). This multisystemic disorder is characterized by intellectual disability,... Show moreZhu-Tokita-Takenouchi-Kim (ZTTK) syndrome is caused by de novo loss-of-function variants in the SON gene (MIM #617140). This multisystemic disorder is characterized by intellectual disability, seizures, abnormal brain imaging, variable dysmorphic features, and various congenital anomalies. The wide application and increasing accessibility of whole exome sequencing (WES) has helped to identify new cases of ZTTK syndrome over the last few years. To date, there have been approximately 45 cases reported in the literature. Here, we describe 15 additional individuals with variants in the SON gene, including those with missense variants bringing the total number of known cases to 60. We have reviewed the clinical and molecular data of these new cases and all previously reported cases to further delineate the most common as well as emerging clinical findings related to this syndrome. Furthermore, we aim to delineate any genotype-phenotype correlations specifically for a recurring pathogenic four base pair deletion (c.5753_5756del) along with discussing the impact of missense variants seen in the SON gene. Show less
We present the first near-IR scattered light detection of the transitional disk associated with the Herbig Ae star MWC 758 using data obtained as part of the Strategic Exploration of Exoplanets... Show moreWe present the first near-IR scattered light detection of the transitional disk associated with the Herbig Ae star MWC 758 using data obtained as part of the Strategic Exploration of Exoplanets and Disks with Subaru, and 1.1 {$μ$}m Hubble Space Telescope/NICMOS data. While submillimeter studies suggested there is a dust-depleted cavity with r = 0.''35, we find scattered light as close as 0.''1 (20-28 AU) from the star, with no visible cavity at H, K', or K$_s$ . We find two small-scaled spiral structures that asymmetrically shadow the outer disk. We model one of the spirals using spiral density wave theory, and derive a disk aspect ratio of h ~{} 0.18, indicating a dynamically warm disk. If the spiral pattern is excited by a perturber, we estimate its mass to be 5$^{+3}$ $_{- 4}$ M$_J$ , in the range where planet filtration models predict accretion continuing onto the star. Using a combination of non-redundant aperture masking data at L' and angular differential imaging with Locally Optimized Combination of Images at K' and K$_s$ , we exclude stellar or massive brown dwarf companions within 300 mas of the Herbig Ae star, and all but planetary mass companions exterior to 0.''5. We reach 5{$σ$} contrasts limiting companions to planetary masses, 3-4 M$_J$ at 1.''0 and 2 M$_J$ at 1.''55, using the COND models. Collectively, these data strengthen the case for MWC 758 already being a young planetary system. Show less
Grady, C.; Muto, T.; Hashimoto, J.; Fukagawa, M.; Currie, T.; Biller, B.; ... ; Tamura, M. 2013
We present the first near-IR scattered light detection of the transitional disk associated with the Herbig Ae star MWC 758 using data obtained as part of the Strategic Exploration of Exoplanets and... Show moreWe present the first near-IR scattered light detection of the transitional disk associated with the Herbig Ae star MWC 758 using data obtained as part of the Strategic Exploration of Exoplanets and Disks with Subaru, and 1.1 {$μ$}m Hubble Space Telescope/NICMOS data. While submillimeter studies suggested there is a dust-depleted cavity with r = 0.''35, we find scattered light as close as 0.''1 (20-28 AU) from the star, with no visible cavity at H, K', or K$_s$ . We find two small-scaled spiral structures that asymmetrically shadow the outer disk. We model one of the spirals using spiral density wave theory, and derive a disk aspect ratio of h ~{} 0.18, indicating a dynamically warm disk. If the spiral pattern is excited by a perturber, we estimate its mass to be 5$^{+3}$ $_{- 4}$ M$_J$ , in the range where planet filtration models predict accretion continuing onto the star. Using a combination of non-redundant aperture masking data at L' and angular differential imaging with Locally Optimized Combination of Images at K' and K$_s$ , we exclude stellar or massive brown dwarf companions within 300 mas of the Herbig Ae star, and all but planetary mass companions exterior to 0.''5. We reach 5{$σ$} contrasts limiting companions to planetary masses, 3-4 M$_J$ at 1.''0 and 2 M$_J$ at 1.''55, using the COND models. Collectively, these data strengthen the case for MWC 758 already being a young planetary system. Show less
