Editorial

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Open AccessEditorial

Special Issue “Diagnosis and Treatment of Rare Diseases”

by Álvaro Hermida-Ameijeiras

J. Clin. Med. 2024, 13(9), 2574; https://doi.org/10.3390/jcm13092574 (registering DOI) - 27 Apr 2024

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Rare diseases (RDs) represent a large and heterogeneous group of low-prevalence conditions, and 473 million people could be affected worldwide [...] Full article

(This article belongs to the Special Issue Diagnosis and Treatment of Rare Diseases)

Research

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10 pages, 753 KiB

Open AccessCommunication

The Clinical Utility of the Saliva Proteome in Rare Diseases: A Pilot Study for Biomarker Discovery in Primary Sclerosing Cholangitis

by Elisa Ceccherini, Elena Michelucci, Giovanni Signore, Barbara Coco, Michela Zari, Massimo Bellini, Maurizia Rossana Brunetto, Antonella Cecchettini and Silvia Rocchiccioli

J. Clin. Med. 2024, 13(2), 544; https://doi.org/10.3390/jcm13020544 - 18 Jan 2024

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Abstract

Background: Primary sclerosing cholangitis (PSC) is a rare chronic inflammatory liver disease characterized by biliary strictures and cholestasis. Due to the lack of effective serological indicators for diagnosis and prognosis, in the present study, we examined the potentiality of the saliva proteome to [...] Read more.

Background: Primary sclerosing cholangitis (PSC) is a rare chronic inflammatory liver disease characterized by biliary strictures and cholestasis. Due to the lack of effective serological indicators for diagnosis and prognosis, in the present study, we examined the potentiality of the saliva proteome to comprehensively screen for novel biomarkers. Methods: Saliva samples of PSC patients and healthy controls were processed and subsequently analyzed using a liquid chromatography–tandem mass spectrometry technique. A bioinformatic approach was applied to detect the differentially expressed proteins, their related biological functions and pathways, and the correlation with the clinical evidence in order to identify a possible marker for the PSC group. Results: We identified 25 differentially expressed proteins in PSC patients when compared to the healthy control group. Among them, eight proteins exhibited area under the curve values up to 0.800, suggesting these saliva proteins as good discriminators between the two groups. Multiple positive correlations were also identified between the dysregulated salivary proteins and increased serum alkaline phosphatase levels and the presence of ulcerative colitis. Pathway analysis revealed significant enrichments in the immune system, neutrophil degranulation, and in the interleukine-17 signaling pathway. Conclusion: We demonstrated the potentiality of saliva as a useful biofluid to obtain a fingerprint of the pathology, suggesting disulfide-isomerase A3 and peroxiredoxin-5 as the better discriminating proteins in PSC patients. Hence, analysis of saliva proteins could become, in future, a useful tool in the screening of patients with suspected PSC. Full article

(This article belongs to the Special Issue Diagnosis and Treatment of Rare Diseases)

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12 pages, 1103 KiB

Open AccessArticle

Clinical Characterisation and Comorbidities of Acquired Generalised Lipodystrophy: A 14-Year Follow-Up Study

by Antia Fernandez-Pombo, Teresa Prado-Moraña, Everardo Josue Diaz-Lopez, Sofia Sanchez-Iglesias, Ana I. Castro, Silvia Cobelo-Gomez and David Araujo-Vilar

J. Clin. Med. 2023, 12(23), 7344; https://doi.org/10.3390/jcm12237344 - 27 Nov 2023

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Abstract

Acquired generalised lipodystrophy (AGL) is a rare disorder characterised by the gradual loss of fat that tends to generalise over time, the origin of which is still not fully clarified. The aim of this study was to offer a detailed description of seven [...] Read more.

Acquired generalised lipodystrophy (AGL) is a rare disorder characterised by the gradual loss of fat that tends to generalise over time, the origin of which is still not fully clarified. The aim of this study was to offer a detailed description of seven patients with AGL (five women, 33.8 ± 18.6 years of age), evaluated over the last 14 years, in order to augment the knowledge of this disorder. The onset of the phenotype occurred during childhood and adolescence in five cases, and in adulthood in two cases. Three patients reported infections or vaccine administration prior to the development of lipodystrophy, and two subjects reported nodular swelling. The most frequent physical features were phlebomegaly, umbilical protrusion/hernia, and acanthosis nigricans. Skinfolds and body composition analysis showed the generalised absence of fat, with the exception of one patient in whom fat loss was spared in the trunk. The loss of fat in the palms/soles was observed in five subjects. Regarding metabolic comorbidities, throughout follow-up, two patients developed type 1 diabetes and one type 2 diabetes; three also presented hypertriglyceridaemia, one of whom developed acute pancreatitis, and no macrovascular complications were observed. Only one patient showed decreased complement C4. Autoimmunity was present in all cases, and six patients manifested Hashimoto’s thyroiditis, type 1 diabetes, autoimmune hepatitis, and/or celiac disease. Thus, there are certain clinical characteristics of AGL that may be considered important diagnostic criteria to differentiate this disorder from other lipodystrophy subtypes. Full article

(This article belongs to the Special Issue Diagnosis and Treatment of Rare Diseases)

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10 pages, 1361 KiB

Open AccessArticle

Neurological and Dermatological Manifestations of Tuberous Sclerosis Complex: Report from a Romanian Tertiary Hospital Cohort

by Adriana Octaviana Dulamea, Anca Adriana Arbune, Daniela Anghel, Voicu Boscaiu, Andreea Andronesi and Gener Ismail

J. Clin. Med. 2023, 12(20), 6550; https://doi.org/10.3390/jcm12206550 - 16 Oct 2023

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Abstract

Tuberous sclerosis complex is a rare multisystem genetic disorder characterized by multiorgan involvement, frequently associated with intellectual impairment and epilepsy. The aim of our study was to describe the neurological and dermatological manifestations of TSC in 32 adult patients (of whom 19 were [...] Read more.

Tuberous sclerosis complex is a rare multisystem genetic disorder characterized by multiorgan involvement, frequently associated with intellectual impairment and epilepsy. The aim of our study was to describe the neurological and dermatological manifestations of TSC in 32 adult patients (of whom 19 were females) who attended the Neurology and Nephrology Clinics of Fundeni Clinical Institute in Romania from 2015 to 2020. Seventeen patients were diagnosed with epilepsy, nine patients had intellectual impairment, and complete neuroimaging was available for twenty-two patients. As expected, the most frequent dermatological lesions were cutaneous angiofibromas in 20 patients, but with a lower frequency than described in the current literature. Statistical analysis was performed considering the small number of patients. Cortical tubers in neuroimaging seemed to be associated with the diagnosis of epilepsy, while subependymal nodules represented a risk factor for intellectual impairment. Males showed a larger number of dermatological types of lesions, especially café -au-lait patches. Interestingly, we found a statistically significant positive association between epilepsy and the presence of cutaneous angiofibromas, as well as total dermatological involvement. Females had significantly higher Charlson comorbidity index scores, indicating a higher burden of disease. Everolimus seemed to be a well-tolerated treatment and showed promising results in controlling epileptic seizures alone in two patients. More studies, with the inclusion of a larger number of patients, are needed to confirm these results. Full article

(This article belongs to the Special Issue Diagnosis and Treatment of Rare Diseases)

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16 pages, 5268 KiB

Open AccessArticle

Morphological Hallmarks of Classical Fabry Disease: An Ultrastructural Study in a Large Spanish Family

by Beatriz San Millán-Tejado, Carmen Navarro, Julián Fernández-Martín, Alberto Rivera, Irene Viéitez, Susana Teijeira and Saida Ortolano

J. Clin. Med. 2023, 12(17), 5689; https://doi.org/10.3390/jcm12175689 - 31 Aug 2023

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Abstract

Fabry disease (FD) is a rare lysosomal disorder caused by α-galactosidase A deficiency, and it leads to the systemic deposition of globotriasylceramide. Demonstrations of the storage material in biopsies support this diagnosis. We report a histological and ultrastructural study of biopsies that were [...] Read more.

Fabry disease (FD) is a rare lysosomal disorder caused by α-galactosidase A deficiency, and it leads to the systemic deposition of globotriasylceramide. Demonstrations of the storage material in biopsies support this diagnosis. We report a histological and ultrastructural study of biopsies that were performed on 11 individuals from a family with the variant p.Gln279Arg in GLA, which is associated with the classical phenotype of Fabry disease. Intralysosomal deposits were found in all biopsies, corresponding to the skin, kidney, and endomyocardium in both sexes and at different ages. In nine of the skin biopsies, deposits were analysed by immunofluorescence and quantified at the ultrastructural level. Then, the findings were compared according to sex, genotype, and treatment. The quantification of the deposits in the skin biopsies revealed a broader involvement in men than in women. A significant clearance of the deposits was observed in one case after treatment. Tissue involvement was remarkable at diagnosis in all individuals. The findings from the skin biopsies were demonstrative of classic FD, thus supporting the diagnosis; repeated biopsy analyses suggested the benefit of early treatment. Full article

(This article belongs to the Special Issue Diagnosis and Treatment of Rare Diseases)

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14 pages, 2009 KiB

Open AccessArticle

Supporting the Diagnosis of Fabry Disease Using a Natural Language Processing-Based Approach

by Adrian A. Michalski, Karol Lis, Joanna Stankiewicz, Sylwester M. Kloska, Arkadiusz Sycz, Marek Dudziński, Katarzyna Muras-Szwedziak, Michał Nowicki, Stanisława Bazan-Socha, Michal J. Dabrowski and Grzegorz W. Basak

J. Clin. Med. 2023, 12(10), 3599; https://doi.org/10.3390/jcm12103599 - 22 May 2023

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Abstract

In clinical practice, the consideration of non-specific symptoms of rare diseases in order to make a correct and timely diagnosis is often challenging. To support physicians, we developed a decision-support scoring system on the basis of retrospective research. Based on the literature and [...] Read more.

In clinical practice, the consideration of non-specific symptoms of rare diseases in order to make a correct and timely diagnosis is often challenging. To support physicians, we developed a decision-support scoring system on the basis of retrospective research. Based on the literature and expert knowledge, we identified clinical features typical for Fabry disease (FD). Natural language processing (NLP) was used to evaluate patients’ electronic health records (EHRs) to obtain detailed information about FD-specific patient characteristics. The NLP-determined elements, laboratory test results, and ICD-10 codes were transformed and grouped into pre-defined FD-specific clinical features that were scored in the context of their significance in the FD signs. The sum of clinical feature scores constituted the FD risk score. Then, medical records of patients with the highest FD risk score were reviewed by physicians who decided whether to refer a patient for additional tests or not. One patient who obtained a high-FD risk score was referred for DBS assay and confirmed to have FD. The presented NLP-based, decision-support scoring system achieved AUC of 0.998, which demonstrates that the applied approach enables for accurate identification of FD-suspected patients, with a high discrimination power. Full article

(This article belongs to the Special Issue Diagnosis and Treatment of Rare Diseases)

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14 pages, 277 KiB

Open AccessArticle

by Anna Rozensztrauch, Izabela Dzien and Robert Śmigiel

J. Clin. Med. 2023, 12(5), 1769; https://doi.org/10.3390/jcm12051769 - 22 Feb 2023

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Abstract

Background: Menkes disease (MD; OMIM #309400) is a progressive neurodegeneration that results from abnormalities in the copper metabolism which are already present before birth. It is an extremely rare condition. The study was conducted to assess the quality of life of children with [...] Read more.

Background: Menkes disease (MD; OMIM #309400) is a progressive neurodegeneration that results from abnormalities in the copper metabolism which are already present before birth. It is an extremely rare condition. The study was conducted to assess the quality of life of children with MD syndrome and the impact of the disease on family functioning. Methods: A cross-sectional questionnaire survey was used. The subjects were 16 parents of children with MD. The method used was the Paediatric Quality of Life Inventory and the PedsQL Family Impact Module and the author’s own questionnaire. Results: Quality of life (QOL) was 29.14 (SD = 14.73), with the lowest for physical functioning (M = 10.55; SD = 10.26) and highest for emotional functioning (M = 48.13; SD = 29.43). The highest score was on the family relationships domain (M = 56.25, SD = 20.38) and the cognitive functioning domain (M = 50.00, SD = 19.24) and the lowest was on the daily activities’ domain (M = 32.29, SD = 20.38) and the physical functioning domain (M = 39.84, SD = 14.90). The analysis did not show statistically significant relationships between age (p = 0.193) and the number of epileptic seizures a week (p = 0.641) and the overall QOL of the children studied. No statistically significant relationships were found between treatment with copper histidine and the overall QOL of the children (p = 0.914) and in physical functioning (p = 0.927), emotional functioning (p = 0.706), and social functioning (p = 0.751). The presence of comorbidities did not have an influence on the overall QOL. Conclusions: MD has a moderate impact on the functioning of the families of the affected children. The age of the child, number of epileptic seizures a week, feeding method (oral feeding or feeding via a PEG tube), and treatment with copper histidine do not have a significant impact on the QOL of children with MD. Full article

(This article belongs to the Special Issue Diagnosis and Treatment of Rare Diseases)

Review

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22 pages, 1584 KiB

Open AccessReview

Advancing the Clinical and Molecular Understanding of Cornelia de Lange Syndrome: A Multidisciplinary Pediatric Case Series and Review of the Literature

by Karolina Gruca-Stryjak, Emilia Doda-Nowak, Julia Dzierla, Karolina Wróbel, Marta Szymankiewicz-Bręborowicz and Jan Mazela

J. Clin. Med. 2024, 13(8), 2423; https://doi.org/10.3390/jcm13082423 - 21 Apr 2024

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Abstract

Cornelia de Lange syndrome (CdLS) is a complex genetic disorder with distinct facial features, growth limitations, and limb anomalies. Its broad clinical spectrum presents significant challenges in pediatric diagnosis and management. Due to cohesin complex mutations, the disorder’s variable presentation requires extensive research [...] Read more.

Cornelia de Lange syndrome (CdLS) is a complex genetic disorder with distinct facial features, growth limitations, and limb anomalies. Its broad clinical spectrum presents significant challenges in pediatric diagnosis and management. Due to cohesin complex mutations, the disorder’s variable presentation requires extensive research to refine care and improve outcomes. This article provides a case series review of pediatric CdLS patients alongside a comprehensive literature review, exploring clinical variability and the relationship between genotypic changes and phenotypic outcomes. It also discusses the evolution of diagnostic and therapeutic techniques, emphasizing innovations in genetic testing, including detecting mosaicism and novel genetic variations. The aim is to synthesize case studies with current research to advance our understanding of CdLS and the effectiveness of management strategies in pediatric healthcare. This work highlights the need for an integrated, evidence-based approach to diagnosis and treatment. It aims to fill existing research gaps and advocate for holistic care protocols and tailored treatment plans for CdLS patients, ultimately improving their quality of life. Full article

(This article belongs to the Special Issue Diagnosis and Treatment of Rare Diseases)

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10 pages, 1421 KiB

Open AccessReview

The Need for Earlier Diagnosis of Obstructed Hemivagina and Ipsilateral Renal Agenesis/Anomaly (OHVIRA) Syndrome in Case of Renal Agenesis in Girls—Case Report and Review of the Literature

by Agnieszka Lecka-Ambroziak, Lidia Skobejko-Włodarska and Hanna Ruta

J. Clin. Med. 2023, 12(23), 7284; https://doi.org/10.3390/jcm12237284 - 24 Nov 2023

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Abstract

Obstructed hemivagina and ipsilateral renal agenesis/anomaly (OHVIRA) syndrome is a very rare condition affecting girls. The time of diagnosis varies, from cases of prenatal diagnosis up to adulthood, including pregnancy or delivery. Most commonly, it is recognised during puberty and usually as an [...] Read more.

Obstructed hemivagina and ipsilateral renal agenesis/anomaly (OHVIRA) syndrome is a very rare condition affecting girls. The time of diagnosis varies, from cases of prenatal diagnosis up to adulthood, including pregnancy or delivery. Most commonly, it is recognised during puberty and usually as an acute condition. We present a case report of an adolescent girl who underwent the treatment because of acute abdominal pain. The case is interesting due to a previous diagnosis of one-side renal agenesis. It appears to be useful to perform a diagnostic pelvic imaging at the time of diagnosis of renal agenesis or to plan to perform it at the beginning of puberty, to prevent the need for urgent surgery. This management may allow the planning of proper follow-up, minimising the risk of possible complications. Full article

(This article belongs to the Special Issue Diagnosis and Treatment of Rare Diseases)

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11 pages, 873 KiB

Open AccessReview

Lysinuric Protein Intolerance and Its Nutritional and Multisystemic Challenges in Pregnancy: A Case Report and Literature Review

by Adriana Pané, Camila Milad, Marta Santana-Domínguez, Núria Baños, Cristina Borras-Novell, Gerard Espinosa, Laura Magnano, Meritxell Nomdedeu, Pedro Juan Moreno-Lozano, Frederic Cofan, Mercè Placeres, Rosa Maria Fernández, Judit García-Villoria, Glòria Garrabou, Irene Vinagre, Laura M. Tanner, Cristina Montserrat-Carbonell and Maria de Talló Forga-Visa

J. Clin. Med. 2023, 12(19), 6405; https://doi.org/10.3390/jcm12196405 - 08 Oct 2023

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Abstract

Lysinuric protein intolerance (LPI) is a rare inborn error of metabolism (IEM), classified as an inherited aminoaciduria, caused by mutations in the SLC7A7 gene, leading to a defective cationic amino acid transport. The metabolic adaptations to the demands of pregnancy and delivery cause [...] Read more.

Lysinuric protein intolerance (LPI) is a rare inborn error of metabolism (IEM), classified as an inherited aminoaciduria, caused by mutations in the SLC7A7 gene, leading to a defective cationic amino acid transport. The metabolic adaptations to the demands of pregnancy and delivery cause significant physiological stress, so those patients affected by IEM are at greater risk of decompensation. A 28-year-old woman with LPI had experienced 3 early miscarriages. While pregnancy was finally achieved, diverse nutritional and medical challenges emerged (food aversion, intrauterine growth restriction, bleeding risk, and preeclampsia suspicion), which put both the mother and the fetus at risk. Moreover, the patient requested a natural childbirth (epidural-free, delayed cord clamping). Although the existence of multiple safety concerns rejected this approach at first, the application of novel strategies made a successful delivery possible. This case reinforces that the woman’s wish for a non-medicated, low-intervention natural birth should not be automatically discouraged because of an underlying complex metabolic condition. Achieving a successful pregnancy is conceivable thanks to the cooperation of interdisciplinary teams, but it is still important to consider the risks beforehand in order to be prepared for possible additional complications. Full article

(This article belongs to the Special Issue Diagnosis and Treatment of Rare Diseases)

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15 pages, 2927 KiB

Open AccessReview

Trofinetide for Rett Syndrome: Highlights on the Development and Related Inventions of the First USFDA-Approved Treatment for Rare Pediatric Unmet Medical Need

by Shuaibu A. Hudu, Fayig Elmigdadi, Aiman Al Qtaitat, Mazen Almehmadi, Ahad Amer Alsaiari, Mamdouh Allahyani, Abdulelah Aljuaid, Magdi Salih, Adel Alghamdi, Mohammad A. Alrofaidi, Abida and Mohd Imran

J. Clin. Med. 2023, 12(15), 5114; https://doi.org/10.3390/jcm12155114 - 04 Aug 2023

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Abstract

Rett syndrome (RTT) is a rare disability causing female-oriented pediatric neurodevelopmental unmet medical need. RTT was recognized in 1966. However, over the past 56 years, the United States Food and Drug Administration (USFDA) has authorized no effective treatment for RTT. Recently, Trofinetide was [...] Read more.

Rett syndrome (RTT) is a rare disability causing female-oriented pediatric neurodevelopmental unmet medical need. RTT was recognized in 1966. However, over the past 56 years, the United States Food and Drug Administration (USFDA) has authorized no effective treatment for RTT. Recently, Trofinetide was approved by the USFDA on 10 March 2023 as the first RTT treatment. This article underlines the pharmaceutical advancement, patent literature, and prospects of Trofinetide. The data for this study were gathered from the PubMed database, authentic websites (Acadia Pharmaceuticals, Neuren Pharmaceuticals, and USFDA), and free patent databases. Trofinetide was first disclosed by Neuren Pharmaceuticals in 2000 as a methyl group containing analog of the naturally occurring neuroprotective tripeptide called glycine-proline-glutamate (GPE). The joint efforts of Acadia Pharmaceuticals and Neuren Pharmaceuticals have developed Trofinetide. The mechanism of action of Trofinetide is not yet well established. However, it is supposed to improve neuronal morphology and synaptic functioning. The patent literature revealed a handful of inventions related to Trofinetide, providing excellent and unexplored broad research possibilities with Trofinetide. The development of innovative Trofinetide-based molecules, combinations of Trofinetide, patient-compliant drug formulations, and precise MECP2-mutation-related personalized medicines are foreseeable. Trofinetide is in clinical trials for some neurodevelopmental disorders (NDDs), including treating Fragile X syndrome (FXS). It is expected that Trofinetide may be approved for treating FXS in the future. The USFDA-approval of Trofinetide is one of the important milestones for RTT therapy and is the beginning of a new era for the therapy of RTT, FXS, autism spectrum disorder (ASD), brain injury, stroke, and other NDDs. Full article

(This article belongs to the Special Issue Diagnosis and Treatment of Rare Diseases)

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Open AccessCase Report

Preparing Enteral Formulas for Adult Patients with Phenylketonuria: A Minor Necessity but Major Challenge—A Case Report

by Adriana Pané, Marcos Carrasco-Serrano, Camila Milad, Pere Leyes, Pedro Juan Moreno-Lozano, Roser Ventura, José Cesar Milisenda, Francesc Josep García-García, Glòria Garrabou, Judit García-Villoria, Rosa Maria López-Galera, Antonia Ribes, Josep Maria Grau-Junyent, Maria de Talló Forga-Visa, Cristina Montserrat-Carbonell and on behalf of PKU.CAT Consortium

J. Clin. Med. 2023, 12(23), 7452; https://doi.org/10.3390/jcm12237452 - 01 Dec 2023

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Abstract

Phenylketonuria (PKU) is the most frequent of the congenital errors of amino acid (AA) metabolism worldwide. It leads to the accumulation of the essential AA phenylalanine (Phe) and it is associated with severe neurological defects. The early diagnosis and treatment of this rare [...] Read more.

Phenylketonuria (PKU) is the most frequent of the congenital errors of amino acid (AA) metabolism worldwide. It leads to the accumulation of the essential AA phenylalanine (Phe) and it is associated with severe neurological defects. The early diagnosis and treatment of this rare disease, achieved through newborn screening and low-Phe diet, has profoundly changed its clinical spectrum, resulting in normal cognitive development. We face the first generation of PKU patients perinatally diagnosed and treated who have reached adulthood, whose special needs must be addressed, including feeding through enteral nutrition (EN). However, recommendations regarding EN in PKU constitute a gap in the literature. Although protein substitutes for patients with PKU are offered in multiple forms (Phe-free L-amino acid or casein glycomacropeptide supplements), none of these commercial formulas ensures the whole provision of daily total energy and protein requirements, including a safe amount of Phe. Consequently, the combination of different products becomes necessary when artificial nutrition via tube feeding is required. Importantly, the composition of these specific formulas may result in physicochemical interactions when they are mixed with standard EN products, leading to enteral feeding tubes clogging, and also gastrointestinal concerns due to hyperosmolality. Herein, we present the first reported case of EN use in an adult patient with PKU, where the separate administration of protein substitutes and the other EN products avoided physicochemical interactions. Full article

(This article belongs to the Special Issue Diagnosis and Treatment of Rare Diseases)

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9 pages, 1452 KiB

Open AccessBrief Report

Association of a Novel Homozygous Variant in ABCA1 Gene with Tangier Disease

by Sofía Barbosa-Gouveia, Silvia Fernández-Crespo, Héctor Lazaré-Iglesias, Arturo González-Quintela, Néstor Vázquez-Agra and Álvaro Hermida-Ameijeiras

J. Clin. Med. 2023, 12(7), 2596; https://doi.org/10.3390/jcm12072596 - 30 Mar 2023

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Abstract

Tangier disease (TD) is a rare autosomal recessive disorder caused by a variant in the ABCA1 gene, characterized by significantly reduced levels of plasma high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A-1 (ApoA-I). TD typically leads to accumulation of cholesterol in the peripheral tissues [...] Read more.

Tangier disease (TD) is a rare autosomal recessive disorder caused by a variant in the ABCA1 gene, characterized by significantly reduced levels of plasma high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A-1 (ApoA-I). TD typically leads to accumulation of cholesterol in the peripheral tissues and early coronary disease but with highly variable clinical expression. Herein, we describe a case study of a 59-year-old male patient with features typical of TD, in whom a likely pathogenic variant in the ABCA1 gene was identified by whole-exome sequencing (WES), identified for the first time as homozygous (NM_005502.4: c.4799A>G (p. His1600Arg)). In silico analysis including MutationTaster and DANN score were used to predict the pathogenicity of the variant and a protein model generated by SWISS-MODEL was built to determine how the homozygous variant detected in our patient may change the protein structure and impact on its function. This case study describes a homozygous variant of the ABCA1 gene, which is responsible for a severe form of TD and underlines the importance of using bioinformatics and genomics for linking genotype to phenotype and better understanding and accounting for the functional impact of genetic variations. Full article

(This article belongs to the Special Issue Diagnosis and Treatment of Rare Diseases)

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