Perceived knowledge, attitudes and practices regarding the medical consortium among medical staff in Sichuan, China: a cross-sectional survey.

BACKGROUND: In China, fragmented and inefficient health care systems are common while quality resources are limited. To promote an organized, efficient system, the government launched a medical consortium policy to vertically integrate health care through the collaboration of different levels of medical care. Logically, medical staff's knowledge, attitudes and practices (KAP) regarding the consortium are critical for its development. The objective of this study was to explore the KAP regarding the medical consortium among medical staff in a medical consortium in Sichuan Province, China. METHODS: A cross-sectional survey was conducted. In total, 690 medical staff members in 3 cities of Sichuan Province, China, were interviewed from November 2018 to December 2018. The questionnaire consisted of 18 items, including 4 items related to perceived knowledge, 4 items related to attitudes and 2 items related to practices, and was rated on a 5-point Likert scale (one = strongly disagree/do not know, five = strongly agree/know). RESULTS: The effective response sample was 640 copies of the questionnaire, and most medical staff members (92.50%) knew about the cooperation with other hospitals in the medical consortium. Medical staff scored differently on each item in the questionnaire, with the highest score being the item 'agreeing with the ward rounds and clinical teaching and training organized by the leading hospital' (4.54 ± 0.76), and the lowest score being the item 'frequency in participating in ward rounds and clinical teaching organized by the leading hospital' (2.83 ± 1.36). In addition, the effect of demographic characteristics on KAP was evaluated by stepwise multiple regression analysis, and a significant positive correlation was found between all the studied variables by Spearman's correlation (p < 0.05). CONCLUSIONS: This study showed that the attitudes toward and knowledge of the medical consortium significantly contribute to practices, satisfaction with the support work performed by the leading hospital and agreement of improvement after joining the medical consortium. Thus, to improve medical staff's KAP and satisfaction, publicity and educational programs in medical consortia are necessary, and the leading hospital should attach importance to the informatization construction and demand of different medical staff members. CLINICAL TRIAL REGISTRATION: There are no clinical trials in this study.

Correction: High-resolution DNA size enrichment using a magnetic nano-platform and application in non-invasive prenatal testing.

Correction for 'High-resolution DNA size enrichment using a magnetic nano-platform and application in non-invasive prenatal testing' by Bo Zhang et al., Analyst, 2020, 145, 5733-5739, DOI: 10.1039/D0AN00813C.

G3viz: an R package to interactively visualize genetic mutation data using a lollipop-diagram.

SUMMARY: The lollipop-diagram is one of the widely used graphical representations to visualize and explore translational effects of genetic mutations in cancer genomics. However, an easy-to-use lollipop-diagram tool with full functionality is still lacking. Here, we introduce g3viz, an R package that enables researchers to explore genetic mutation data using a lollipop-diagram in a web browser. With a few lines of R code, users can interactively visualize data details, annotate findings and export resultant diagrams in high-quality figures. Because of usefulness and usability, g3viz can be generally exploited by researchers with different levels of bioinformatics skills and programming experience. AVAILABILITY AND IMPLEMENTATION: The R package is freely available under the MIT license from CRAN (http://cran.r-project.org/web/packages/g3viz). The g3lollipop JavaScript package is freely available under MIT license at GitHub (https://github.com/g3viz/g3lollipop.js). SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

High-resolution DNA size enrichment using a magnetic nano-platform and application in non-invasive prenatal testing.

Precise DNA sizing can boost sequencing efficiency, reduce cost, improve data quality, and even allow sequencing of low-input samples, while current pervasive DNA sizing approaches are incapable of differentiating DNA fragments under 200 bp with high resolution (<20 bp). In non-invasive prenatal testing (NIPT), the size distribution of cell-free fetal DNA in maternal plasma (main peak at 143 bp) is significantly different from that of maternal cell-free DNA (main peak at 166 bp). The current pervasive workflow of NIPT and DNA sizing is unable to take advantage of this 20 bp difference, resulting in sample rejection, test inaccuracy, and restricted clinical utility. Here we report a simple, automatable, high-resolution DNA size enrichment workflow, named MiniEnrich, on a magnetic nano-platform to exploit this 20 bp size difference and to enrich fetal DNA fragments from maternal blood. Two types of magnetic nanoparticles were developed, with one able to filter high-molecular-weight DNA with high resolution and the other able to recover the remaining DNA fragments under the size threshold of interest with >95% yield. Using this method, the average fetal fraction was increased from 13% to 20% after the enrichment, as measured by plasma DNA sequencing. This approach provides a new tool for high-resolution DNA size enrichment under 200 bp, which may improve NIPT accuracy by rescuing rejected non-reportable clinical samples, and enable NIPT earlier in pregnancy. It also has the potential to improve non-invasive screening for fetal monogenic disorders, differentiate tumor-related DNA in liquid biopsy and find more applications in autoimmune disease diagnosis.

The health service capacity of primary health care in West China: different perspectives of physicians and their patients.

BACKGROUND: Many countries, including China, have identified the primary health care system as a reform priority. The purpose of this study is to compare the perceived service capacity of primary care from the perspectives of physicians and their patients in Sichuan province of China. METHODS: A cross-sectional survey was conducted through Quality and Costs of Primary Care (QUALICOPC) questionnaires. A representative sample of 319 primary care physicians and 641 patients in 48 primary healthcare settings were recruited to take part in the study. RESULTS: Physicians perceived equity of care the best, while quality of care was rated the highest from the perspective of patients. They both regarded coordination as the weakest dimension of primary care service capacity. CONCLUSIONS: Although primary health care reform may have been effective in helping patients acquire better primary care services, our results suggest that coordination is still perceived to be problematic for both physicians and patients. Improving the coordination of care has to be one of the main goals in the future primary care reforms in China.

Enhanced utility of family-centered diagnostic exome sequencing with inheritance model-based analysis: results from 500 unselected families with undiagnosed genetic conditions.

PURPOSE: Diagnostic exome sequencing was immediately successful in diagnosing patients in whom traditional technologies were uninformative. Herein, we provide the results from the first 500 probands referred to a clinical laboratory for diagnostic exome sequencing. METHODS: Family-based exome sequencing included whole-exome sequencing followed by family inheritance-based model filtering, comprehensive medical review, familial cosegregation analysis, and analysis of novel genes. RESULTS: A positive or likely positive result in a characterized gene was identified in 30% of patients (152/500). A novel gene finding was identified in 7.5% of patients (31/416). The highest diagnostic rates were observed among patients with ataxia, multiple congenital anomalies, and epilepsy (44, 36, and 35%, respectively). Twenty-three percent of positive findings were within genes characterized within the past 2 years. The diagnostic rate was significantly higher among families undergoing a trio (37%) as compared with a singleton (21%) whole-exome testing strategy. CONCLUSION: Overall, we present results from the largest clinical cohort of diagnostic exome sequencing cases to date. These data demonstrate the utility of family-based exome sequencing and analysis to obtain the highest reported detection rate in an unselected clinical cohort, illustrating the utility of diagnostic exome sequencing as a transformative technology for the molecular diagnosis of genetic disease.

ELP2 is a novel gene implicated in neurodevelopmental disabilities.

Elongator is a multi-subunit protein complex essential to transcription elongation, histone acetylation, and tRNA modification. The complex consists of six highly conserved protein subunits, called Elongator Proteins (ELP) 1-6. Apart from an association with intellectual disability (ID), there is limited clinical information about patients with ELP2 variants. Here we report on two brothers with severe ID, spastic diplegia, and self-injury whose presentation eluded a diagnosis for over 20 years. In both brothers, whole exome sequencing revealed a likely pathogenic, compound heterozygous missense variant in ELP2. We describe the phenotype and natural history of the ELP2-related disorder in these brothers.

New Insights into the Genetics of Fetal Megacystis: ACTG2 Mutations, Encoding γ-2 Smooth Muscle Actin in Megacystis Microcolon Intestinal Hypoperistalsis Syndrome (Berdon Syndrome).

OBJECTIVE: To identify the molecular basis for prenatally suspected cases of megacystis microcolon intestinal hypoperistalsis syndrome (MMIHS) (MIM 249210) in 3 independent families with clinical and radiographic evidence of MMIHS. METHODS: Whole-exome sequencing (WES) and Sanger sequencing of the ACTG2 gene. RESULTS: We identified a novel heterozygous de novo missense variant in ACTG2 c.770G>A (p.Arg257His) encoding x03B3;-2 smooth muscle actin (ACTG2) in 2 siblings with MMIHS, suggesting gonadal mosaicism of one of the parents. Two additional de novo missense variants (p.Arg257Cys and p.Arg178His) in ACTG2 were identified in 2 additional MMHIS patients. All of our patients had evidence of fetal megacystis and a normal or slightly increased amniotic fluid volume. Additional findings included bilateral renal hydronephrosis, an enlarged fetal stomach, and transient dilated bowel loops. ACTG2 immunostaining of the intestinal tissue showed an altered muscularis propria, a markedly thinned longitudinal muscle layer, and a reduced amount and abnormal distribution of ACTG2. CONCLUSION: Our study demonstrates that de novo mutations in ACTG2 are a cause of fetal megacystis in MMIHS and that gonadal mosaicism may be present in a subset of cases. These findings have implications for the counseling of families with a diagnosis of fetal megacystis with a preserved amniotic fluid volume and associated gastrointestinal findings.

Expanding the clinical and mutational spectrum of Kaufman oculocerebrofacial syndrome with biallelic UBE3B mutations.

Biallelic mutations of UBE3B have recently been shown to cause Kaufman oculocerebrofacial syndrome (also reported as blepharophimosis-ptosis-intellectual disability syndrome), an autosomal recessive condition characterized by hypotonia, developmental delay, intellectual disability, congenital anomalies, characteristic facial dysmorphic features, and low cholesterol levels. To date, six patients with either missense mutations affecting the UBE3B HECT domain or truncating mutations have been described. Here, we report on the identification of homozygous or compound heterozygous UBE3B mutations in six additional patients from five unrelated families using either targeted UBE3B sequencing in individuals with suggestive facial dysmorphic features, or exome sequencing. Our results expand the clinical and mutational spectrum of the UBE3B-related disorder in several ways. First, we have identified UBE3B mutations in individuals who previously received distinct clinical diagnoses: two sibs with Toriello-Carey syndrome as well as the patient reported to have a "new" syndrome by Buntinx and Majewski in 1990. Second, we describe the adult phenotype and clinical variability of the syndrome. Third, we report on the first instance of homozygous missense alterations outside the HECT domain of UBE3B, observed in a patient with mildly dysmorphic facial features. We conclude that UBE3B mutations cause a clinically recognizable and possibly underdiagnosed syndrome characterized by distinct craniofacial features, hypotonia, failure to thrive, eye abnormalities, other congenital malformations, low cholesterol levels, and severe intellectual disability. We review the UBE3B-associated phenotypes, including forms that can mimick Toriello-Carey syndrome, and suggest the single designation "Kaufman oculocerebrofacial syndrome".

Advancements in the ERK1/2 Signaling Pathway Affecting Male Reproduction.

Male infertility, age-related changes, and tumors have been increasingly studied in the field of male reproductive health due to the emergence of environmental stressors, declining fertility rates, and aging populations. Numerous studies have demonstrated that the ERK1/2 signaling pathway plays a significant role in male reproduction. The ERK1/2 pathway is associated with several signaling pathways and has a complex interplay that influences the spermatogenic microenvironment, sperm viability, gonadal axis regulation, as well as resistance to testicular aging and tumors. Moreover, the ERK1/2 pathway directly or indirectly regulates testicular somatic cells, which are crucial for maintaining spermatogenesis and microenvironment regulation. Given the critical role of the ERK1/2 signaling pathway in male reproductive health, comprehensive exploration of its multifaceted effects on male reproduction and underlying mechanisms is necessary. This study aims to provide a solid foundation for in-depth research in the field of male reproduction and further enhance the reproductive health of males.

Pharmacovigilance analysis of orlistat adverse events based on the FDA adverse event reporting system (FAERS) database.

Objective: Based on the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) database, we analyzed the signals of potential adverse events (AEs) of orlistat in the real world to provide a reference for its safe clinical use. Methods: The FAERS database and OpenVigil 2.1 were used to obtain data on adverse events of orlistat from the first quarter of 2004 to the first quarter of 2023, and to analyze the population in which the adverse events occurred. And the signals of their potential adverse events were mined using reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN) and empirical Bayesian geometric mean (EBGM). Result: A total of 21,079 reports of adverse events with orlistat as the primary suspected drug were collected in this study. Using four disproportionate analyses, we screened 117 preferred terms (PTs) involving 18 system organ classes (SOCs). We found that the most common adverse events at SOC level for orlistat remained "gastrointestinal disorders", while "metabolism and nutrition disorders", "renal and urinary disorders", "musculoskeletal and connective tissue disorders" and "hepatobiliary disorders" also ranked high in the number of case reports. In addition, at the PT level, we identified several new signals of adverse events not mentioned in the specification, including "lipiduria", "anal haemorrhage", "rectal haemorrhage", "haematochezia", "sigmoiditis", "diverticulitis" and "muscle spasms". Conclusion: Most of the adverse events found in this study are consistent with the results described in the drug label. At the same time, we also found some new adverse events, which require more prospective studies to verify and elucidate their relationship with orlistat.

Fatigue of an Aluminum Foam Sandwich Formed by Powder Metallurgy.

In this paper, an aluminum foam sandwich (AFS) was prepared by the rolling composite-powder metallurgy method, and its fatigue properties were studied. It was compared with an AFS made by the adhesive method to study its fatigue properties more directly. In this experiment, the fatigue performance was investigated by studying the microscopic interface, fatigue life, deflection curve, and failure mode. The results show that the fatigue life of an AFS with the rolling composite-powder metallurgy method is much longer than that with the adhesive method. The failure mode of an AFS made by the rolling composite-powder metallurgy method is shear failure, and that of an AFS made by the adhesive method is shear failure and interface debonding. An AFS with the rolling composite-powder metallurgy method has better fatigue properties. This paper also explored the fatigue damage model using the fatigue modulus method, and the polynomial fitting method has a higher fitting degree.

Multi-functional Strategy: Ammonium Citrate-Modified SnO2 ETL for Efficient and Stable Perovskite Solar Cells.

The tin oxide (SnO2) electron transport layer (ETL) plays a crucial role in perovskite solar cells (PSCs). However, the heterogeneous dispersion of commercial SnO2 colloidal precursors is far from optimized, resulting in dissatisfied device performance with SnO2 ETL. Herein, a multifunctional modification material, ammonium citrate (TAC), is used to modify the SnO2 ETL, bringing four benefits: (1) due to the electrostatic interaction between TAC molecules and SnO2 colloidal particles, more uniformly dispersed colloidal particles are obtained; (2) the TAC molecules distributed on the surface of SnO2 provide nucleation sites for the perovskite film growth, promoting the vertical growth of the perovskite crystal; (3) TAC-doped SnO2 shows higher electron conductivity and better film quality than pristine SnO2 while offering better energy-level alignment with the perovskite layer; and (4) TAC has functional groups of C═O and N-H containing lone pair electrons, which can passivate the defects on the surface of SnO2 and perovskite films through chemical bonding and inhibit the device hysteresis. In the end, the device based on TAC-doped ETL achieved an increased power conversion efficiency (PCE) of 21.58 from 19.75% of the reference without such treatment. Meanwhile, the PSCs using the TAC-doped SnO2 as the ETL maintained 88% of their initial PCE after being stored for about 1000 h under dark conditions and controlled RH of 10-25%.

The Contributing Factors of Delayed-Onset Post-traumatic Stress Disorder Symptoms: A Nested Case-Control Study Conducted After the 2008 Wenchuan Earthquake.

Background: Delayed-onset post-traumatic stress disorder after catastrophes is a major public health issue. However, good designs for identifying post-traumatic stress disorder (PTSD) among earthquake survivors are rare. This is the first nested case-control study to explore the possible factors associated with delayed-onset PTSD symptoms. Methods: A nested case-control study was conducted. The baseline (2011) and follow-up (2018) surveys were utilized to collect data. A total of 361 survivors of the Wenchuan earthquake were investigated and 340 survivors underwent follow-up. The survivors, from the hardest-hit areas, who met the criteria for PTSD were included in the case group, and PTSD-free survivors from the same area, matched for age, were included in the control group, with a ratio of one to four. Conditional logistic regression was used to evaluate the variables' odds ratio (OR). Results: The overall prevalence of delayed-onset PTSD symptoms in survivors of the Wenchuan earthquake was 9.7% (33/340). The unemployed earthquake survivors had a higher risk of developing delayed-onset PTSD symptoms (OR = 4.731, 95% CI = 1.408-15.901), while higher perceived social support was a protective factor against delayed-onset PTSD symptoms (OR = 0.172, 95% CI = 0.052-0.568). Conclusion: Delayed-onset PTSD symptoms, after a disaster, should not be ignored. Active social support and the provision of stable jobs can contribute to the earthquake survivors' mental health.

Risk factors of post-traumatic stress disorder 10 years after Wenchuan earthquake: a population-based case-control study.

AIMS: To investigate the prevalence of post-traumatic stress disorder (PTSD) symptoms in the hard-hit areas 10 years after the Wenchuan earthquake, and explore the risk factors of long-term PTSD among Wenchuan earthquake survivors. METHODS: A matched case-control study was conducted. The involving participants were from the hard-hit areas 10 years after the Wenchuan earthquake. The collected information includes demographic characteristics, socioeconomic status, behaviour habits, earthquake exposure, perceived social support, physical health and mental health. Mental health status was measured using the PTSD Checklist-Civilian Version (PCL-C). Respondents with PCL-C score ⩾38 were classified as cases, and then the cases and controls were matched based on age (±3 years) and community location according to a ratio of 1:3. RESULTS: We obtained 86 cases and 258 controls. After controlling for confounding factors, it was found that lower income (OR 2.42; 95% CI 1.16-5.03), chronic diseases (OR 3.00; 95% CI 1.31-6.88) and death of immediate families in the earthquake (OR 7.30; 95% CI 2.36-22.57) were significantly associated with long-term PTSD symptoms. CONCLUSION: Even 10 years after the Wenchuan earthquake, the survivors in the hard-hit areas still suffered from severe mental trauma. Low income, chronic diseases and death of immediate families in the earthquakes are significantly associated with long-term PTSD symptoms. Interventions by local governments and health institutions to address these risk factors should be undertaken to promote the health of survivors.

Prevalence and Influencing Factors of Post-Traumatic Stress Disorder Among Survivors in the Hard-Hit Areas Ten Years After the Wenchuan Earthquake: A Cross-Sectional Study.

BACKGROUND: Post-traumatic stress disorder (PTSD) is common psychological distress after natural disasters, which is persistent. Chronic PTSD leads to a heavy disease burden. The purpose of this study is to explore the prevalence and influencing factors of chronic PTSD among survivors in the hard-hit areas ten years after the Wenchuan earthquake. MATERIALS AND METHODS: A cross-sectional survey was conducted on residents aged 16 or above in hard-hit areas through a multi-stage sampling approach ten years after the Wenchuan earthquake. The items of the questionnaire included demographic characteristics and earthquake exposure factors, and the PTSD Checklist-Civilian Version (PCL-C) was used to evaluate the PTSD of the respondents. RESULTS: A total of 1039 complete questionnaires were obtained. The median age of 1039 respondents was 60 years, 63.2% of whom were female, 70.2% were illiterate or had received primary education, and 58% had an annual household income of less than 20,000 yuan (US$ 2871.3). The rate of PTSD was 9.1% (95/1039). After controlling for confounding factors, it was found that higher income level and education level, and moving to concentrated rural settlement (CRS) after the earthquake might be protective factors for the long-term mental health of survivors in the hard-hit areas, and the loss of immediate families in the earthquake was an important risk factor. CONCLUSION: Even though ten years have passed since the Wenchuan earthquake, the survivors in the hard-hit areas still have a serious mental disorder. The local government and health-care institutions should take appropriate measures to improve the mental health of residents.

Neurexin 1alpha structural variants associated with autism.

Neurexins are presynaptic membrane cell-adhesion molecules which bind to neuroligins, a family of proteins that are associated with autism. To explore the possibility that structural variants in the neurexin alpha genes predispose to autism, the coding regions and associated splice junctions of the neurexin 1alpha gene were sequenced in 116 Caucasian patients with autism and 192 Caucasian controls. Five ultra-rare structural variants including a predicted splicing mutation were found in patients with autism and absent in 10,000 control alleles. Only one ultra-rare structural variant was found in controls (5/116 vs. 1/192; P=0.03, Fisher's exact test, one-sided). In the context of all available data, the ultra-rare structural variants of the neurexin 1alpha gene are consistent with mutations predisposing to autism.

Genetic analysis of the GRIK2 modifier effect in Huntington's disease.

BACKGROUND: In Huntington's disease (HD), age at neurological onset is inversely correlated with the length of the CAG trinucleotide repeat mutation, but can be modified by genetic factors beyond the HD gene. Association of a relatively infrequent 16 TAA allele of a trinucleotide repeat polymorphism in the GRIK2 3'UTR with earlier than expected age at neurological onset has been suggested to reflect linkage disequilibrium with a functional polymorphism in GRIK2 or an adjacent gene. RESULTS: We have tested this hypothesis by sequencing all GRIK2 exons, the exon-flanking sequences and 3'UTR in several individuals who were crucial to demonstrating the modifier effect, as they showed much earlier age at neurological onset than would be expected from the length of their HD CAG mutation. Though ten known SNPs were detected, no sequence variants were found in coding or adjacent sequence that could explain the modifier effect by linkage disequilibrium with the 16 TAA allele. Haplotype analysis using microsatellites, known SNPs and new variants discovered in the 3'UTR argues against a common ancestral origin for the 16 TAA repeat alleles in these individuals. CONCLUSION: These data suggest that the modifier effect is actually due to the TAA repeat itself, possibly via a functional consequence on the GRIK2 mRNA.

Diagnostic Exome Sequencing and Tailored Bioinformatics of the Parents of a Deceased Child with Cobalamin Deficiency Suggests Digenic Inheritance of the MTR and LMBRD1 Genes.

Disorders of cobalamin deficiency are a heterogeneous group of disorders with at least 19 autosomal recessive-associated genes. Familial samples of an infant who died due to presumed cobalamin deficiency were referred for clinical exome sequencing. The patient died before obtaining a blood sample or skin biopsy, autopsy was declined, and DNA yielded from the newborn screening blood spot was insufficient for diagnostic testing. Whole-exome sequencing of the mother, father, and unaffected sister and tailored bioinformatics analysis was applied to search for mutations in underlying disorders with recessive inheritance. This approach identified alterations within two genes, each of which was carried by one parent. The mother carried a missense alteration in the MTR gene (c.3518C>T; p.P1173L) which was absent in the father and the sister. The father carried a translational frameshift alteration in the LMBRD1 gene (c.1056delG; p.L352Lfs*18) which was absent in the mother and present in the heterozygous state in the sister. These mutations in the MTR (MIM# 156570) and LMBRD1 (MIM# 612625) genes have been described in patients with disorders of cobalamin metabolism complementation groups cblG and cblF, respectively. The child's clinical presentation and biochemical results demonstrated overlap with both cblG and cblF. Sanger sequencing using DNA from the infant's blood spot confirmed the inheritance of the two alterations in compound heterozygous form. We present the first example of exome sequencing leading to a diagnosis in the absence of the affected patient. Furthermore, the data support the possibility for potential digenic inheritance associated with cobalamin deficiency.

Congenital lethal motor neuron disease with a novel defect in ribosome biogenesis.

OBJECTIVE: We describe a novel congenital motor neuron disease with early demise due to respiratory insufficiency with clinical overlap with spinal muscular atrophy with respiratory distress (SMARD) type 1 but lacking a mutation in the IGHMBP2 gene. METHODS: Exome sequencing was used to identify a de novo mutation in the LAS1L gene in the proband. Pathogenicity of the mutation was validated using a zebrafish model by morpholino-mediated knockdown of las1l. RESULTS: We identified a de novo mutation in the X-linked LAS1L gene in the proband (p.S477N). The mutation is in a highly conserved region of the LAS1L gene predicted to be deleterious by bioinformatic analysis. Morpholino-based knockdown of las1l, the orthologous gene in zebrafish, results in early lethality and disruption of muscle and peripheral nerve architecture. Coinjection of wild-type but not mutant human RNA results in partial rescue of the phenotype. CONCLUSION: We report a patient with a SMARD phenotype due to a mutation in LAS1L, a gene important in coordinating processing of the 45S pre-rRNA and maturation of the large 60S ribosomal subunit. Similarly, the IGHMB2 gene associated with SMARD type 1 has been suggested to have an important role in ribosomal biogenesis from its role in processing the 45S pre-rRNA. We propose that disruption of ribosomal maturation may be a common pathogenic mechanism linking SMARD phenotypes caused by both IGHMBP2 and LAS1L.