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BACKGROUND: Chronic cough, a cough lasting >8 weeks, includes refractory chronic cough (RCC) and unexplained chronic cough (UCC). Patient-reported outcome (PRO) measures are needed to better understand chronic cough impacts that matter most to patients. The 19-item Leicester Cough Questionnaire (LCQ), an existing PRO measure of chronic cough, assesses impacts of cough across physical, psychological, and social domains. However, the content validity of the LCQ evaluating these concepts in patients with RCC/UCC had not been established. OBJECTIVES: To evaluate the content validity of the LCQ in patients with RCC/UCC. DESIGN: A cross-sectional, qualitative interview study. METHODS: First, previously completed qualitative interview results in adults with RCC/UCC (N = 30) were evaluated and mapped to LCQ concepts. Next, a clinical cough expert reviewed each LCQ item and assessed the salience of its concepts for patients with RCC/UCC. Finally, semistructured interviews-including both concept elicitation and cognitive debriefing-were conducted in adults with RCC/UCC (N = 20) to elicit a comprehensive set of participant experiences and to assess the appropriateness of using the LCQ in this population. RESULTS: Concepts reported in the past and present qualitative interviews were included across all LCQ items, and most impacts reported to be the "most bothersome" were assessed in the LCQ. In the current study, all participants indicated that reduced cough frequency would be an important treatment target. During cognitive debriefing, each LCQ item was endorsed by ⩾70% of participants. Additionally, participants were generally able to understand, recall, and select a response for each LCQ item. All participants and the clinical expert indicated that the LCQ was appropriate and assessed the impacts most relevant to patients with RCC/UCC. CONCLUSION: Our findings support the content validity of the LCQ and demonstrate that this measure is fit-for-purpose and includes important cough impacts in adults with RCC/UCC.

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Phelan-McDermid syndrome (PMS) is a rare genetic neurodevelopmental disorder that results from the loss of one functional copy of the SHANK3 gene. While many clinical features of PMS are well-understood, there is currently limited literature on cardiovascular abnormalities in PMS. This report aims to evaluate the prevalence of aortic root dilation (ARD) among individuals with PMS and to understand if underlying genetic variation relates to risk for ARD. We present findings from 59 participants collected from a multisite observational study evaluating the phenotype and natural history of PMS. Individual echocardiographic and genetic reports were analyzed for aortic root measurements and genetic variant data, respectively. Our a priori hypothesis was that participants with chromosome 22 deletions with hg19 start coordinates on or before 49,900,000 (larger deletions) would have more instances of ARD than participants with deletion start coordinates after 49,900,000 (smaller deletions). Eight participants (14%) had ARD, and its presence was statistically significantly associated with large deletions (p = 0.047). Relatedly, participants with ARD had significantly more genes deleted on chromosome 22 than participants without ARD (p = 0.013). These results could aid in the identification of individuals with PMS who are at higher risk for ARD.

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In 2010, the United States Human and Health Services (US HHS) and the European Union's (EU) Directorate General for Communications Networks, Content and Technology signed a memorandum of understanding to stimulate cooperation surrounding health-related information communications technology. The key project that emerged from this agreement is the International Patient Summary (IPS), intended to provide succinct clinically relevant patient summaries, which are generalizable and condition-independent, that can be readily used by all clinicians for the care of patients. Although allergies are included in the main information required by the IPS library and framework, it is misrepresented which leads to underdiagnosis or misdiagnosis of patients suffering from allergic and hypersensitivity conditions (A/H). The French and Montpellier World Health Organization (WHO) Collaborating Centres have provided arguments for supporting representation of A/H in the IPS. These are based on the relevance of the new classification of A/H in the WHO International Classification of Diseases 11th version (ICD-11), and the need for alignment of eHealth tools with harmonized health information. We first present the A/H in the IPS initiative with the mission of producing an international information system that can be used globally in electronic health records to standardize clinical diagnoses and facilitate communication between clinicians caring for patients with A/H diseases. It is believed this initiative will provide a strong voice for the allergy community and an effective process for improving the quality of health data that will optimize medical care for our patients worldwide.

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The presence of angioedema, or deep skin swelling, in addition to hives (wheals) in patients with chronic spontaneous urticaria (CSU) can complicate disease management. There is evidence that omalizumab is effective for patients with CSU with angioedema, but the time to a clinically meaningful response has not been assessed. This post hoc analysis examined data from the phase 3, randomized, double-blind ASTERIA I and ASTERIA II studies: patients with CSU with hives were grouped by presence (n = 216) or absence of angioedema (n = 265) at baseline. The time to minimally important difference (MID, change from baseline of ≥11 points) in weekly Urticaria Activity Score (UAS7) was analyzed using Kaplan-Meier analyses. Median time to MID for omalizumab 300 mg was similar in patients with and without angioedema. Median time to MID for omalizumab 150 mg was similar to 300 mg for patients without angioedema, and was longer for patients with angioedema. Therefore, the response to omalizumab for patients with CSU with angioedema was dose dependent. We recommend that the best approach for clinicians, in line with guidelines, would be initial administration of omalizumab 300 mg every 4 weeks for all patients. Clinical trials registration: Clinicaltrials.gov NCT01287117 (registered 27 January 2011) and NCT01292473 (registered 7 February 2011).

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BACKGROUND: Lanadelumab was well-tolerated and effective in preventing hereditary angioedema (HAE) attacks in the phase 3, double-blind, placebo-controlled HELP Study and subsequent open-label extension study, HELP OLE (NCT02741596). OBJECTIVE: To evaluate outcomes from HELP OLE for adolescent patients aged 12 to 17 years. METHODS: HELP OLE comprised patients who completed the HELP Study (rollovers) and new eligible (lanadelumab-naive) patients. Rollovers received a single dose of lanadelumab 300 mg at the last HELP Study visit (day 0). Treatment was then paused until patients experienced their first investigator-confirmed HAE attack, following which lanadelumab 300 mg was administered every 2 weeks (Q2W) for up to 33 months (4 weeks/month). Lanadelumab-naive patients received lanadelumab 300 mg Q2W from day 0. Patient-reported outcomes included Angioedema Quality of Life Questionnaire (AE-QoL). Safety was monitored throughout the study. RESULTS: The subgroup analysis included 21 patients (8 rollovers, 13 lanadelumab-naive patients); 95.2% completed ≥ 30 months on study. Mean (SD) monthly attack rates decreased from 1.58 (1.0) at baseline to 0.11 (0.2) during treatment (mean 94.7% reduction). Eight (38.1%) patients were attack-free during treatment and, on average, 99.1% of days were attack-free (mean 27.7 days/month). Patients reported a mean (SD) AE-QoL total score of 27.5 (17.5) at baseline vs 7.5 (13.2) at end of study. Twelve (57.1%) patients reported treatment-related treatment-emergent adverse events; however, there were no treatment-related serious adverse events. CONCLUSION: Lanadelumab provided long-term efficacy in preventing HAE attacks, was associated with clinically meaningful improvements in health-related quality of life and high levels of treatment satisfaction, and was well-tolerated in adolescent patients.

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Importance: Although treatment for chronic urticaria (CU) has improved over the past decades, evidence regarding costs and net benefits associated with these treatment strategies have yet to be comprehensively characterized and synthesized. Objective: To summarize the cost and cost-effectiveness of CU management strategies. Evidence Review: An extensive systematic literature search of 6 databases (MEDLINE, Embase, PubMed Cochrane, Scopus, and CINAHL) and gray literature sources, without language restriction, was conducted and updated to March 23, 2024. Articles that performed cost analysis or full economic evaluation among patients with CU were included. Two reviewers independently extracted data, such as annual costs of health care services or incremental cost-effectiveness ratio (ICER) per quality-adjusted life-year (QALY). All monetary values were converted and inflated to 2023 US dollars. Evidence-based synthesis for health benefit was judged using the Evidence Rating Matrix by the Institute for Clinical and Economic Review. Findings: Seventeen unique studies (11 cost analysis studies and 6 full economic evaluations) were included. With the wide variation in health care resources, services that included biologic omalizumab utilization had higher annual health care cost estimations for CU management than services that did not include omalizumab prescription (median [IQR] cost, $6933 [$5988-$8717] vs $5621 [$2488-$8754]). The biologic omalizumab, 300 mg, for H1 antihistamine-refractory chronic spontaneous urticaria (CSU) (3 studies) was found to have a median (IQR) ICER of $89 005 ($36 058-$145 694) per QALY (evidence rating as incremental or better; moderate certainty with substantial net health benefit). Routine laboratory testing among patients with CSU with otherwise normal histories and physical examination findings (1 study) had ICERs ranging from $1 427 928 to $1 950 524 per QALY (evidence rating as comparable or inferior; moderate certainty that the net health benefit is inferior). Conclusions and Relevance: With limited evidence of cost-effectiveness, biologic omalizumab, 300 mg, for H1 antihistamine-refractory CSU was found to be cost-effective in US health care services at the willingness to pay threshold of $150 000 per QALY. Meanwhile, routine laboratory testing among patients with CSU without compelling indication was not cost-effective. Future studies in more diverse CU populations and resource settings are needed to fill evidence gaps.

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Reducing the burden of disease for patients and families requires being able to measure health status changes related to disease severity, control, and response to treatment over time. Patient-reported outcomes are patient perceptions of their health status. Such perceptions are critical to decision making. Some patient-reported outcome measures (PROMs) are extensive and often intended to be used only for detailed research assessments. Many PROMs, however, form critical components of valid, reliable, and responsive assessments in clinical research and routine clinical practice. The smallest score change in a PROM that would lead to different decision making by patients is called the minimally important difference. Using PROMs may also offer advantages over general questions or unvalidated tools. With the innovation of technology, the ability to chronicle disease symptoms using communication technology (mobile phone applications) has become increasingly available. Collection of real-world data in this capacity will be very useful for identifying more precise phenotypes/endotypes necessary for investigation of tailored therapies for chronic spontaneous and inducible urticaria, angioedema, and atopic dermatitis. Here, we provide an overview of PROMs that have been developed for the assessment of disease severity, control, and quality of life and that have been validated for the use of adults and children with these skin disorders.

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Around 60% of individuals with neurodevelopmental disorders (NDD) remain undiagnosed after comprehensive genetic testing, primarily of protein-coding genes1. Large genome-sequenced cohorts are improving our ability to discover new diagnoses in the non-coding genome. Here we identify the non-coding RNA RNU4-2 as a syndromic NDD gene. RNU4-2 encodes the U4 small nuclear RNA (snRNA), which is a critical component of the U4/U6.U5 tri-snRNP complex of the major spliceosome2. We identify an 18 base pair region of RNU4-2 mapping to two structural elements in the U4/U6 snRNA duplex (the T-loop and stem III) that is severely depleted of variation in the general population, but in which we identify heterozygous variants in 115 individuals with NDD. Most individuals (77.4%) have the same highly recurrent single base insertion (n.64_65insT). In 54 individuals in whom it could be determined, the de novo variants were all on the maternal allele. We demonstrate that RNU4-2 is highly expressed in the developing human brain, in contrast to RNU4-1 and other U4 homologues. Using RNA sequencing, we show how 5' splice-site use is systematically disrupted in individuals with RNU4-2 variants, consistent with the known role of this region during spliceosome activation. Finally, we estimate that variants in this 18 base pair region explain 0.4% of individuals with NDD. This work underscores the importance of non-coding genes in rare disorders and will provide a diagnosis to thousands of individuals with NDD worldwide.

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PURPOSE: Can certain characteristics identify as solvable some undiagnosed patients who seek extensive evaluation and thorough record review, such as by the Undiagnosed Diseases Network (UDN)? METHODS: The UDN is a national research resource to solve medical mysteries through team science. Applicants provide informed consent to access to their medical records. After review, expert panels assess if applicants meet inclusion and exclusion criteria to select participants. When not accepting applicants, UDN experts may offer suggestions for diagnostic efforts. Using minimal information from initial applications, we compare features in applicants who are not accepted with those who are accepted and either solved or still not solved by the UDN. The diagnostic suggestions offered to nonaccepted applicants and their clinicians were tallied. RESULTS: Nonaccepted applicants were more often female, older at first symptoms and application, and longer in review compared with accepted applicants. The accepted and successfully diagnosed applicants were younger, shorter in review time, more often non-White, of Hispanic ethnicity, and presenting with nervous system features. Half of nonaccepted applicants were given suggestions for further local diagnostic evaluation. A few seemed to have 2 major diagnoses or a provocative environmental exposure history. CONCLUSION: Comprehensive UDN record review generates possibly helpful advice.

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BACKGROUND: Nasal polyps (NPs) are commonly associated with chronic rhinosinusitis (CRS). In keeping with the unified airway hypothesis, asthma and CRS with NP (CRSwNP) frequently co-occur, share a similar pathophysiology, and are often treated with oral corticosteroids (OCS); however, a need for alternative treatment options for patients with comorbid asthma and CRSwNP remains. OBJECTIVE: To characterize the short- and long-term dual airway effectiveness of the anti-interleukin-5 monoclonal antibody, mepolizumab, in real-world patients with asthma and comorbid NP. METHODS: Adult patients with CRSwNP who initiated mepolizumab from November 1, 2014, to September 30, 2021, were identified from 2 Merative MarketScan Research Databases. Outcomes were compared for the 12 months pre- and post-mepolizumab initiation and a variable follow-up period. Primary outcomes included the following: annual rate and proportion of patients with NP- and asthma-related exacerbations; NP surgery occurrences; all-cause OCS claims, number of OCS bursts, and daily OCS dose; all-cause and NP-related health care resource utilization. RESULTS: During the 12 months post-index, patients experienced fewer NP- and asthma-related exacerbations, required fewer sinus surgeries, and reduced use of OCS, with fewer all-cause OCS claims and OCS bursts. Significant reductions in asthma exacerbation-related and NP-related health care resource utilization were also observed. CONCLUSION: This study illustrated the near- and long-term real-world effectiveness of mepolizumab treatment, with a focus on dual lower and upper airway benefit from single-agent add-on therapy. These results may aid physicians in clinical decision-making for patients with asthma and comorbid CRSwNP with complex care needs.

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Leucine aminoacyl tRNA-synthetase 1 (LARS1)-deficiency (infantile liver failure syndrome type 1 (ILFS1)) has a multisystemic phenotype including fever-associated acute liver failure (ALF), chronic neurologic abnormalities, and encephalopathic episodes. In order to better characterize encephalopathic episodes and MRI changes, 35 cranial MRIs from 13 individuals with LARS1 deficiency were systematically assessed and neurological phenotype was analyzed. All individuals had developmental delay and 10/13 had seizures. Encephalopathic episodes in 8/13 were typically associated with infections, presented with seizures and reduced consciousness, mostly accompanied by hepatic dysfunction, and recovery in 17/19 episodes. Encephalopathy without hepatic dysfunction occurred in one individual after liver transplantation. On MRI, 5/7 individuals with MRI during acute encephalopathy had deep gray matter and brainstem changes. Supratentorial cortex involvement (6/13) and cerebellar watershed injury (4/13) occurred with seizures and/or encephalopathy. Abnormal brainstem contour on sagittal images (8/13), atrophy (8/13), and myelination delay (8/13) were not clearly associated with encephalopathy. The pattern of deep gray matter and brainstem changes are apparently characteristic of encephalopathy in LARS1-deficiency, differing from patterns of hepatic encephalopathy or metabolic stroke in organic acidurias and mitochondrial diseases. While the pathomechanism remains unclear, fever and energy deficit during infections might be causative; thus, sufficient glucose and protein intake along with pro-active fever management is suggested. As severe episodes were observed during influenza infections, we strongly recommend seasonal vaccination.

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Neuropsychiatric symptoms have long been acknowledged as a common comorbidity for individuals with allergic diseases. The proposed mechanisms for this relationship vary by disease and patient population and may include neuroinflammation and/or the consequent social implications of disease symptoms and management. We review connections between mental health and allergic rhinitis, atopic dermatitis, asthma, vocal cord dysfunction, urticaria, and food allergy. Many uncertainties remain and warrant further research, particularly with regard to how medications interact with pathophysiologic mechanisms of allergic disease in the neuroimmune axis. Proactive screening for mental health challenges, using tools such as the Patient Health Questionnaire and Generalized Anxiety Disorder screening instruments among others, can aid clinicians in identifying patients who may need further psychiatric evaluation and support. Although convenient, symptom screening tools are limited by variable sensitivity and specificity and therefore require healthcare professionals to remain vigilant for other mental health "red flags." Ultimately, understanding the connection between allergic disease and mental health empowers clinicians to both anticipate and serve the diverse physical and mental health needs of their patient populations.

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A minority of patients with autism spectrum disorder (ASD) are offered genetic testing by their providers or referred for genetics evaluation despite published guidelines and consensus statements supporting genetics-informed care for this population. This study aimed to investigate the ordering habits of providers of different specialties and to additionally assess the diagnostic utility of genetic testing by test type, patient sex, and race and ethnicity. We retrospectively analyzed data associated with orders for the indication of ASD from a large clinical laboratory over 6 years (2017-2022). Geneticists and neurologists were more likely than other specialists to order exome sequencing and neurodevelopmental (NDD) panel testing while other providers were more likely to order chromosomal microarray (CMA) and Fragile X testing. Exome had the highest diagnostic yield (24.5%), followed by NDD panel (6.4%), CMA (6.2%), and Fragile X testing (0.4%). Females were 1.4x (95% CI: 1.2-1.7) more likely than males to receive a genetic diagnosis. However, for Fragile X, males had a higher diagnostic yield than females (0.4% vs 0.2%). Our findings highlight the need to enable non-genetics providers to order comprehensive genetic testing or promote referral to genetics following negative CMA and/or Fragile X testing. Our data supports that ASD testing should include exome, CMA, and other clinically indicated tests, as first-tier tests, with the consideration of panel testing, in cases where exome sequencing is not an option. Lastly, our study helps to inform expectations for genetic testing yield by test type and patient presentation.

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Chronic urticaria is an inflammatory skin disorder defined by the presence of evanescent erythematous pruritic wheals, angioedema, or both. While treatment guidelines are continuing to become more clearly defined, there is still a gap in the medical literature surrounding chronic spontaneous urticaria (CSU) treatment in vulnerable populations such as children (aged 0-18 years), pregnant women, and the elderly (aged >65 years). The purpose of this review is to provide an update on CSU in each of these special population categories by defining prevalence, identifying diagnostic considerations, and exploring current and future management options.

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BACKGROUND: The benefits and harms of adding antileukotrienes to H1 antihistamines (AHs) for the management of urticaria (hives, itch, and/or angioedema) remain unclear. OBJECTIVE: We sought to systematically synthesize the treatment outcomes of antileukotrienes in combination with AHs versus AHs alone for acute and chronic urticaria. METHODS: As part of updating American Academy of Allergy, Asthma & Immunology and American College of Allergy, Asthma, and Immunology Joint Task Force on Practice Parameters urticaria guidelines, we searched Medline, Embase, Central, LILACS, WPRIM, IBECS, ICTRP, CBM, CNKI, VIP, Wanfang, US Food and Drug Administration, and European Medicines Agency databases from inception to December 18, 2023, for randomized controlled trials (RCTs) evaluating antileukotrienes and AHs versus AHs alone in patients with urticaria. Paired reviewers independently screened citations, extracted data, and assessed risk of bias. Random effects models pooled effect estimates for urticaria activity, itch, wheal, sleep, quality of life, and harms. The GRADE approach informed certainty of evidence ratings. The study was registered at the Open Science Framework (osf.io/h2bfx/). RESULTS: Thirty-four RCTs enrolled 3324 children and adults. Compared to AHs alone, the combination of a leukotriene receptor antagonist with AHs probably modestly reduces urticaria activity (mean difference, -5.04; 95% confidence interval, -6.36 to -3.71; 7-day urticaria activity score) with moderate certainty. We made similar findings for itch and wheal severity as well as quality of life. Adverse events were probably not different between groups (moderate certainty); however, no RCT reported on neuropsychiatric adverse events. CONCLUSION: Among patients with urticaria, adding leukotriene receptor antagonists to AHs probably modestly improves urticaria activity with little to no increase in overall adverse events. The added risk of neuropsychiatric adverse events in this population with leukotriene receptor antagonists is small and uncertain.

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BACKGROUND: Topical corticosteroids are widely used as a treatment for itch and wheals (urticaria), but their benefits and harms are unclear. OBJECTIVE: To systematically synthesize the benefits and harms of topical corticosteroids for the treatment of urticaria. METHODS: We searched MEDLINE, EMBASE, and CENTRAL from database inception to March 23, 2024, for randomized trials comparing topical corticosteroids with placebo for patients with urticaria (either chronic spontaneous or inducible urticaria or acute urticaria elicited from skin/intradermal allergy testing). Paired reviewers independently screened records, extracted data, and assessed risk of bias. Random-effects meta-analyses addressed urticaria severity, itch severity (numeric rating scale; range 0-10; higher is worse), and adverse events. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach informed certainty of evidence ratings. PROSPERO registration: CRD42023455182. RESULTS: A total of 19 randomized controlled trials enrolled 379 participants with a median of mean age of 30.1 (range 21.1-44.0) years. Compared with placebo, topical corticosteroids may reduce wheal size (ratio of means 0.47, 95% CI 0.38-0.59; low certainty) and itch severity (mean difference -1.30, 95% CI -5.07 to 2.46; very low certainty). Topical corticosteroids result in little to no difference in overall adverse events (94 fewer patients per 1000, 95% credible intervals 172 fewer to 12 more; high certainty). CONCLUSION: Compared with placebo, topical corticosteroids may result in a reduction of wheal size and little to no difference in overall adverse events. Topical corticosteroids may reduce itch severity, but the evidence is very uncertain. Future large, randomized trials addressing the use of topical corticosteroids would further support optimal urticaria management.

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Transcriptomics is a powerful tool for unraveling the molecular effects of genetic variants and disease diagnosis. Prior studies have demonstrated that choice of genome build impacts variant interpretation and diagnostic yield for genomic analyses. To identify the extent genome build also impacts transcriptomics analyses, we studied the effect of the hg19, hg38, and CHM13 genome builds on expression quantification and outlier detection in 386 rare disease and familial control samples from both the Undiagnosed Diseases Network and Genomics Research to Elucidate the Genetics of Rare Disease Consortium. Across six routinely collected biospecimens, 61% of quantified genes were not influenced by genome build. However, we identified 1,492 genes with build-dependent quantification, 3,377 genes with build-exclusive expression, and 9,077 genes with annotation-specific expression across six routinely collected biospecimens, including 566 clinically relevant and 512 known OMIM genes. Further, we demonstrate that between builds for a given gene, a larger difference in quantification is well correlated with a larger change in expression outlier calling. Combined, we provide a database of genes impacted by build choice and recommend that transcriptomics-guided analyses and diagnoses are cross referenced with these data for robustness.

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Nucleic acid-sensing Toll-like receptors (TLR) 3, 7/8, and 9 are key innate immune sensors whose activities must be tightly regulated to prevent systemic autoimmune or autoinflammatory disease or virus-associated immunopathology. Here, we report a systematic scanning-alanine mutagenesis screen of all cytosolic and luminal residues of the TLR chaperone protein UNC93B1, which identified both negative and positive regulatory regions affecting TLR3, TLR7, and TLR9 responses. We subsequently identified two families harboring heterozygous coding mutations in UNC93B1, UNC93B1+/T93I and UNC93B1+/R336C, both in key negative regulatory regions identified in our screen. These patients presented with cutaneous tumid lupus and juvenile idiopathic arthritis plus neuroinflammatory disease, respectively. Disruption of UNC93B1-mediated regulation by these mutations led to enhanced TLR7/8 responses, and both variants resulted in systemic autoimmune or inflammatory disease when introduced into mice via genome editing. Altogether, our results implicate the UNC93B1-TLR7/8 axis in human monogenic autoimmune diseases and provide a functional resource to assess the impact of yet-to-be-reported UNC93B1 mutations.

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PURPOSE: The function of FAM177A1 and its relationship to human disease is largely unknown. Recent studies have demonstrated FAM177A1 to be a critical immune-associated gene. One previous case study has linked FAM177A1 to a neurodevelopmental disorder in 4 siblings. METHODS: We identified 5 individuals from 3 unrelated families with biallelic variants in FAM177A1. The physiological function of FAM177A1 was studied in a zebrafish model organism and human cell lines with loss-of-function variants similar to the affected cohort. RESULTS: These individuals share a characteristic phenotype defined by macrocephaly, global developmental delay, intellectual disability, seizures, behavioral abnormalities, hypotonia, and gait disturbance. We show that FAM177A1 localizes to the Golgi complex in mammalian and zebrafish cells. Intersection of the RNA sequencing and metabolomic data sets from FAM177A1-deficient human fibroblasts and whole zebrafish larvae demonstrated dysregulation of pathways associated with apoptosis, inflammation, and negative regulation of cell proliferation. CONCLUSION: Our data shed light on the emerging function of FAM177A1 and defines FAM177A1-related neurodevelopmental disorder as a new clinical entity.

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