Molecular Syndromology最新文献

{"title":"Reanalysis of Chromosomal Microarray Data Using a Smaller Copy Number Variant Call Threshold Identifies Four Cases with Heterozygous Multiexon Deletions of ARID1B, EHMT1, and FOXP1 Genes.","authors":"Noriko Kubota, Ryojun Takeda, Jun Kobayashi, Eiko Hidaka, Eriko Nishi, Kyoko Takano, Keiko Wakui","doi":"10.1159/000530252","DOIUrl":"10.1159/000530252","url":null,"abstract":"<p><strong>Introduction: </strong>Chromosomal microarray (CMA) is a highly accurate and established method for detecting copy number variations (CNVs) in clinical genetic testing. CNVs are important etiological factors for disorders such as intellectual disability, developmental delay, and multiple congenital anomalies. Recently developed analytical methods have facilitated the identification of smaller CNVs. Therefore, reanalyzing CMA data using a smaller CNV calling threshold may yield useful information. However, this method was left to the discretion of each institution.</p><p><strong>Methods: </strong>We reanalyzed the CMA data of 131 patients using a smaller CNV call threshold: 50 kb 50 probes for gain and 25 kb 25 probes for loss. We interpreted the reanalyzed CNVs based on the most recently available information. In the reanalysis, we filtered the data using the Clinical Genome Resource dosage sensitivity gene list as an index to quickly and efficiently check morbid genes.</p><p><strong>Results: </strong>The number of copy number loss was approximately 20 times greater, and copy number gain was approximately three times greater compared to those in the previous analysis. We detected new likely pathogenic CNVs in four participants: a 236.5 kb loss within <i>ARID1B</i>, a 50.6 kb loss including <i>EHMT1</i>, a 46.5 kb loss including <i>EHMT1</i>, and an 89.1 kb loss within the <i>FOXP1</i> gene.</p><p><strong>Conclusion: </strong>The method employed in this study is simple and effective for CMA data reanalysis using a smaller CNV call threshold. Thus, this method is efficient for both ongoing and repeated analyses. This study may stimulate further discussion of reanalysis methodology in clinical laboratories.</p>","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":"14 1","pages":"394-404"},"PeriodicalIF":1.1,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10601822/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42080086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extensive, 3.8 Mb-Sized Deletion of 22q12 in a Patient with Bilateral Schwannoma, Intellectual Disability, Sensorineural Hearing Loss, and Epilepsy.","authors":"Jakub Trizuljak, Jakub Duben, Ivona Blaháková, Zuzana Vrzalová, Kateřina Staňo Kozubík, Jiří Štika, Lenka Radová, Veronika Bergerová, Soňa Mejstříková, Věra Hořínová, Radim Jančálek, Šárka Pospíšilová, Michael Doubek","doi":"10.1159/000528744","DOIUrl":"10.1159/000528744","url":null,"abstract":"<p><strong>Introduction: </strong>In contrast with the well-known and described deletion of the 22q11 chromosome region responsible for DiGeorge syndrome, 22q12 deletions are much rarer. Only a few dozen cases have been reported so far. This region contains genes responsible for cell cycle control, chromatin modification, transmembrane signaling, cell adhesion, and neural development, as well as several cancer predisposition genes.</p><p><strong>Case presentation: </strong>We present a patient with cleft palate, sensorineural hearing loss, vestibular dysfunction, epilepsy, mild to moderate intellectual disability, divergent strabism, pes equinovarus, platyspondylia, and bilateral schwannoma. Using Microarray-based Comparative Genomic Hybridization (aCGH), we identified the de novo 3.8 Mb interstitial deletion at 22q12.1→22q12.3. We confirmed deletion of the critical <i>NF2</i> region by MLPA analysis.</p><p><strong>Discussion: </strong>Large 22q12 deletion in the proband encases the critical <i>NF2</i> region, responsible for development of bilateral schwannoma. We compared the phenotype of the patient with previously reported cases. Interestingly, our patient developed cleft palate even without deletion of the <i>MN1</i> gene, deemed responsible in previous studies. We also strongly suspect the <i>DEPDC5</i> gene deletion to be responsible for seizures, consistent with previously reported cases.</p>","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":"14 5","pages":"439-448"},"PeriodicalIF":1.1,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10613852/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71427986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel <i>SYNGAP1</i> Variant in an Adult Individual Affected by Intellectual Disability and Epilepsy: A Cold Case Solved through Whole-Exome Sequencing.","authors":"Giulia Rosti, Silvia Boeri, Maria Teresa Divizia, Livia Pisciotta, Maria Margherita Mancardi, Margherita Lerone, Maria Cerminara, Martina Servetti, Giovanni Spirito, Diego Vozzi, Marco Fontana, Stefano Gustincich, Lino Nobili, Federico Zara, Aldamaria Puliti","doi":"10.1159/000529408","DOIUrl":"10.1159/000529408","url":null,"abstract":"<p><strong>Introduction: </strong>Nowadays, whole-exome sequencing (WES) analysis is an essential part in the diagnostic pathway of individuals with complex phenotypes when routine exams, such as array-CGH and gene panels, have proved inconclusive. However, data on the diagnostic rate of WES analysis in adult individuals, negative to first-tier tests, are lacking. This is because initiatives with the aim of diagnosing rare diseases focus mainly on pediatric unsolved cases.</p><p><strong>Case presentation: </strong>We hereby present a 45-year-old woman with severe intellectual disability, previous psychomotor developmental delay, behavioral disorders, stereotypies, nonconvulsive epilepsy, and dysmorphisms. The proband first came to our attention when she was 4 years old (in 1982); since then, she has undergone several clinical and instrumental assessments, without reaching a genetic diagnosis. At last, through WES analysis, a novel de novo variant in <i>SYNGAP1</i> was found. The clinical characteristics associated with <i>SYNGAP1</i> are similar to those presented by the proband.</p><p><strong>Conclusion: </strong>The variant is predicted to be deleterious and is most probably the cause of the proband's phenotype. The perseverance of the clinicians and the family allowed us to reach a diagnosis in a woman with a more than 30-year history of clinical evaluations, instrumental assessments, and genetic tests. This diagnosis was of significant relevance in genetic counseling for family members and the proband herself.</p>","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":"14 5","pages":"433-438"},"PeriodicalIF":1.1,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10617251/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71427987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Description of Phenotypic Heterogeneity in a <i>GJC2</i>-Related Family and Literature Review.","authors":"Aida Ghasemi, Ali Reza Tavasoli, Mana Khojasteh, Mohammad Rohani, Afagh Alavi","doi":"10.1159/000529678","DOIUrl":"10.1159/000529678","url":null,"abstract":"<p><strong>Introduction: </strong>Homozygous and compound heterozygous variants in <i>GJC2</i>, the gene encoding connexin-47 protein, cause Pelizaeus-Merzbacher-like disease type 1 or hypomyelinating leukodystrophy 2 (HLD2), a severe infantile-onset hypomyelinating leukodystrophy, and rarely some milder phenotypes like hereditary spastic paraplegia (HSP) type 44 (SPG44) and subclinical leukodystrophy. Herein, we report an Iranian <i>GJC2</i>-related family with intrafamilial phenotypic heterogeneity and review the literatures.</p><p><strong>Methods: </strong>Whole-exome sequencing was performed for an Iranian proband, who was initially diagnosed as HSP case. Data were analyzed and the candidate variant was confirmed by PCR and Sanger sequencing subsequently checked in family members to co-segregation analysis. A careful clinical and paraclinical evaluation of all affected individuals of the family was done and compared with previous reported <i>GJC2</i>-related families.</p><p><strong>Results: </strong>A novel homozygous variant, c.G14T:p.Ser5Ile, in the <i>GJC2</i> gene was identified. The variant was co-segregated with the disease status in the family members. Clinical evaluation of all patients showed two distinct <i>GJC2</i>-related phenotypes in this family; the proband presented a complicated form of HSP, whereas both his affected sisters presented a HLD2 phenotype.</p><p><strong>Discussion: </strong>Up to now, correlation between HSP and <i>GJC2</i> variants has been reported once. Here, the second case of SPG44 was identified that emphasizes on <i>GJC2</i> as a HSP-causing gene. So, the screening of <i>GJC2</i> in patients with HSP or HSP-like phenotypes especially with hypomyelination in their brain MRI is recommended. Also, for the first time, intrafamilial phenotypic heterogeneity for \"two distinct <i>GJC2</i>-related phenotypes: HLD2 and HSP\" was reported. Such intrafamilial phenotypic heterogeneity for <i>GJC2</i> can emphasize on the shared pathophysiology of these disorders.</p>","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":"14 1","pages":"405-415"},"PeriodicalIF":1.1,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10617252/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48655432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of High-Risk Single Nucleotide Polymorphisms in the Human CYB5R3 Gene Responsible for Recessive Congenital Methemoglobinemia: A Computational Approach.","authors":"Emna Bouatrous, Sonia Nouira, Samia Menif, Houyem Ouragini","doi":"10.1159/000530173","DOIUrl":"10.1159/000530173","url":null,"abstract":"<p><strong>Introduction: </strong>NADH-cytochrome b5 reductase deficiency due to pathogenic variants in the CYB5R3 gene causes recessive congenital methemoglobinemia (RCM) type I or type II. In type I, cyanosis from birth is the only major symptom, and the enzyme deficiency is restricted only to erythrocytes. Whereas in type II, cyanosis is associated with severe neurological manifestations, and the enzyme deficiency is generalized to all tissues.</p><p><strong>Methods: </strong>In this study, several computational methods (SIFT, Polyphen-2, PROVEAN, Mutation Assessor, Panther, Phd-SNP, SNPs&GO, SNAP2, Align, GVGD, MutPred2, I-Mutant 2.0, MUpro, Duet, ConSurf and Netsurf-2.0 tools) were used to find the most deleterious nsSNPs in the <i>CYB5R3</i> gene. Furthermore, structural analysis by Swiss-PDB viewer, protein-ligand docking using FTSite, and protein-protein interaction using STRING were carried out to evaluate the impact of these nsSNPs on the protein structure and function.</p><p><strong>Results: </strong>Our in silico analysis suggested that out of 339 nsSNPs of the <i>CYB5R3</i> gene, 17 (L47H, L47P, R61P, L73R G76D, G76C, P96H, G104C, S128P, G144D, P145S, L149P, Y151H, M177T, I178T, I216N, and G251V), are the most deleterious. Among them, two (P96H and S128P) were reported to be associated with the severe form RCM type II, six are related to RCM type I (G104C, G144D, P145S, L149P, M177T, and I178T), and the remaining nine high-risk nsSNPs have not yet been reported in RCM patients.</p><p><strong>Discussion: </strong>This study highlighted the potential pathogenic nsSNPs of the <i>CYB5R3</i> gene. To comprehend how these most harmful nsSNPs contribute to disease, it is crucial to experimentally validate their functional effects.</p>","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":"14 5","pages":"375-393"},"PeriodicalIF":1.1,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10601824/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71414854","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Triple-A Syndrome in Morocco: Founder Effect, Age Estimation of the &lt;i&gt;AAAS&lt;/i&gt; c.1331+1G&amp;gt;A Variant, and Implications for Genetic Diagnosis","authors":"Karam Yahya Belmokhtar, Imane Cherkaoui, Saida Lhousni, Mounia Elidrissi Errahhali, Manal Elidrissi Errahhali, Majida Charif, Redouane Boulouiz, Meryem Ouarzane, Aziza Elouali, Ayad Ghanam, Abdeladim Babakhouya, Maria Rkain, Noufissa Benajiba, Mohammed Bellaoui","doi":"10.1159/000533894","DOIUrl":"https://doi.org/10.1159/000533894","url":null,"abstract":"<b><i>Introduction:</i></b> Triple-A syndrome (Triple-A) is an autosomal recessive disorder characterized by alacrimia, achalasia, and adrenal insufficiency. Several variants on the <i>AAAS</i> gene have been described, and some variants are clustered in particular geographical areas, such as the c.1331+1G&amp;gt;A variant which is very frequent in North Africa. Here, we describe the genetic features of Triple-A in a series of unrelated families from Morocco. <b><i>Methods:</i></b> Screening for the <i>AAAS</i> c.1331+1G&amp;gt;A variant was performed by direct sequencing or by PCR-RFLP. Haplotype analysis using Single Tandem Repeat (STR) markers flanking <i>AAAS</i> gene was performed in order to evaluate the founder effect and estimate the age of the c.1331+1G&amp;gt;A variant. <b><i>Results:</i></b> Seven unrelated families with ten individuals clinically diagnosed with Triple-A were evaluated for sequence variations in the <i>AAAS</i> gene. The median age at diagnosis was 3 years, with a range between 2 and 11 years. Molecular analysis revealed that all patients were homozygous for the c.1331+1G&amp;gt;A variant. This variant was not found in 200 healthy controls, indicating that carriers are very rare in the general Moroccan population. Subsequently, STR marker analysis revealed a founder effect and that the most recent common ancestor of Triple-A patients in Morocco would have lived 125 years ago. <b><i>Conclusion:</i></b> This is the largest series of Triple-A in Morocco. The same <i>AAAS</i> c.1331+1G&amp;gt;A variant was found in all patients, suggesting a founder effect in Morocco which was subsequently confirmed by microsatellite marker analysis. Therefore, this variant should be systematically investigated to diagnose Triple-A in Morocco.","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":"6 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135296406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expanding the Phenotypic and Genotypic Spectrum of Weaver Syndrome: A Missense Variant of the &lt;i&gt;EZH2&lt;/i&gt; Gene","authors":"Yasemin Kendir-Demirkol, Burcu Yeter, Laura A. Jenny","doi":"10.1159/000533733","DOIUrl":"https://doi.org/10.1159/000533733","url":null,"abstract":"<b><i>Introduction:</i></b> Weaver syndrome (WS) is a rare autosomal dominant disorder characterized by distinctive facial features, pre- and post-natal overgrowth, macrocephaly, and variable developmental delay. The characteristic facial features are ocular hypertelorism, a broad forehead, almond-shaped palpebral fissures and, in early childhood, large, fleshy ears, a pointed “stuck-on” chin with horizontal skin creases, and retrognathia. Heterozygous pathogenic/likely pathogenic variants in the enhancer of zeste homolog 2 (<i>EZH2</i>) gene are responsible for WS. <b><i>Case Presentation:</i></b> Here, we report a male patient with a heterozygous likely pathogenic variant in EZH2 gene who has tall stature, distinctive facial features, mild development delay, hypoxic-ischemic encephalopathy with a MRI finding of periventricular leukomalacia, gingival hypertrophy, and early onset high hypermetropia. <b><i>Conclusion:</i></b> This case demonstrates the importance of reporting detailed molecular and clinical findings in patients to expand the genotypic and phenotypic findings of this rare syndrome.","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":"10 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135470311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prenatal Diagnosis of a de novo 2q14.3-q22.1 Deletion with Complex Chromosomal Rearrangement","authors":"Yong Wu, Chuanning Liao, Yamei Xie, Lingxi Wang","doi":"10.1159/000531769","DOIUrl":"https://doi.org/10.1159/000531769","url":null,"abstract":"<b><i>Introduction:</i></b> Chromosomal aberrations due to complex chromosomal rearrangements (CCRs) can cause abnormal phenotypes if accompanied by microdeletions or microduplications near the breakpoint, or gene breaks. <b><i>Case Presentation:</i></b> We report a prenatal diagnostic case of 2q14.3-q22.1 deletion with ultrasound suggestive of absent nasal bone accompanied by CCRs involving 6 chromosomes. Cytogenetic analysis revealed a karyotype of 46,XY,der(1)t(1;2)(p13.3;p11.2),der(2)t(1;2)inv(2)(q12q14.2)del(2)(q14.3q22.1),t(12;16)(q21.2;q12.1),t(13;21)(q32;q22.1). Chromosomal microarray analysis identified a 14.90 Mb deletion on 2q14.3q22.1. The copy number variant was de novo, as determined by karyotype analysis of the parents’ peripheral blood G-banding. <b><i>Conclusion:</i></b> The region contains haploinsufficient genes that can cause different phenotypes, mainly associated with neurodevelopmental and autism spectrum disorders. However, the genotype-phenotype correlation is limited in prenatal evaluation. Therefore, the combined use of multiple diagnostic techniques has an important role in the assessment of CCRs and genetic counseling.","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":"31 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135255991","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis of Dopamine Receptor D2 Gene Polymorphism and Correlation with Dyslipidemia in the Chinese Population","authors":"Haibo Tan, Zhixue Wang, Jiaxuan Zhang, Maohua Huang, Jide Chen, Fengqi Li, Liangjun Tang","doi":"10.1159/000533637","DOIUrl":"https://doi.org/10.1159/000533637","url":null,"abstract":"<b><i>Objective:</i></b> The study aimed to explore the genotype and allele distributions of dopamine D2-like receptor (<i>DRD2</i>) gene -141C and C957T polymorphisms in the Chinese Han population with dyslipidemia, as well as their association with serum lipid levels. <b><i>Methods:</i></b> One hundred fifty patients with dyslipidemia and 150 healthy people were recruited as the case and the control groups, respectively. Serum total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol levels were detected. The target sequence of <i>DRD2</i> polymorphisms was amplified by polymerase chain reaction and genotyped via Sanger sequencing. <b><i>Results:</i></b> In <i>DRD2</i> gene C957T (rs6277), three genotypes of CC, CT, and TT were detected with the frequencies of 92.67%, 6.67%, 0.67% in dyslipidemia cases, and 83.33%, 14.67%, 2.00% in the controls, respectively. The CT genotype and T allele frequencies were significantly low in the case group relative to the control group. After adjusting to other clinical indicators, the CT genotype of C957T polymorphism (hazard ratio = 0.401, 95% confidence interval = 0.181–0.890, <i>p</i> &amp;lt; 0.05) was still related to a significantly reduced risk of dyslipidemia. The C957T CT genotype carriers had the lowest values of serum TC, TG, LDL, and the highest values of serum HDL-C. <b><i>Conclusion:</i></b> <i>DRD2</i> gene C957T polymorphism was an independent influencing factor associated with the susceptibility to dyslipidemia, and the CT genotype was associated with decreased odds of susceptibility to dyslipidemia.","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":"54 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135787225","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel Insights from Clinical Practice: Xia-Gibbs Syndrome with Pes Cavus, Conjunctival Melanosis, and Eye Asymmetry due to a de novo AHDC1 Gene Variant – A Case Report and a Brief Review of the Literature","authors":"Margherita Baga, Ivan Ivanovski, Gianluca Contrò, Stefano Giuseppe Caraffi, Carlotta Spagnoli, Carlo Alberto Cesaroni, Alberto Neri, Francesca Peluso, Marzia Pollazzon, Livia Garavelli, Carlo Fusco","doi":"10.1159/000530410","DOIUrl":"https://doi.org/10.1159/000530410","url":null,"abstract":"<b><i>Introduction:</i></b> Xia-Gibbs syndrome (OMIM 615829) is a rare developmental disorder, caused by heterozygous de novo variants in the <i>AHDC1</i> gene. Hallmark features include global developmental delay, facial dysmorphisms, and behavioral problems. To date, more than 250 individuals have been diagnosed worldwide. <b><i>Case Report:</i></b> We report a 13-year-old female who, in association with typical features of Xia-Gibbs syndrome, presented with macrocrania, pes cavus, and conjunctival melanosis. Whole-exome sequencing identified a de novo frameshift variant, which had not been reported in the literature before. <b><i>Conclusion:</i></b> We summarized the main clinical and phenotypic features of patients described in the literature, and in addition, we discuss another feature found in our patient and observed in other cases described, eye asymmetry, which has never been highlighted, and suggest that it could be part of the typical clinical presentation of this condition.","PeriodicalId":48566,"journal":{"name":"Molecular Syndromology","volume":"39 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136299697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}