《分子综合征》发表关于常见和罕见遗传综合征的高质量研究文章、简短报告和评论，旨在通过分子见解增加临床理解。特别感兴趣的主题是遗传综合征的分子基础、基因型-表型相关性、自然史、疾病管理策略和基于分子发现的新治疗方法。对模型系统的研究也受到欢迎，特别是当它明显与人类遗传学相关时。通过对当前主题的高质量评论，该杂志旨在促进将研究结果转化为临床环境，同时促进对临床相关问题的进一步研究。该杂志不仅针对医学遗传学家和基础生物医学研究人员，还针对处理遗传综合征的临床医生。该杂志拥有来自三大洲的四位副主编和一个广泛的国际编辑委员会，欢迎投稿，涵盖来自世界各地的最新研究。

The journal "Molecular Syndromology" publishes high-quality research articles, brief reports, and reviews on common and rare genetic syndromes, aiming to enhance clinical understanding through molecular insights. Topics of particular interest include the molecular basis of genetic syndromes, genotype-phenotype correlations, natural history, disease management strategies, and new therapeutic approaches based on molecular discoveries. Research on model systems is also welcomed, especially when it is significantly related to human genetics. Through high-quality reviews on current topics, the journal aims to facilitate the translation of research findings into clinical settings while promoting further investigation into clinically relevant issues. The journal is not only targeted at medical geneticists and basic biomedical researchers but also welcomes submissions from clinicians dealing with genetic syndromes. It boasts four deputy editors from three continents and a broad international editorial board, inviting submissions of the latest research from around the world.

《Molecular Syndromology》期刊发表关于常见和罕见遗传综合征的高质量研究文章、简短报告和评论，旨在通过分子视角增强临床理解。特别关注的主题包括遗传综合征的分子基础、基因型-表型相关性、自然史、疾病管理策略以及基于分子发现的新治疗方法。对模型系统的研究也受到欢迎，尤其是那些与人类遗传学显著相关的研究。通过对当前主题的高质量评论，该杂志旨在促进研究成果向临床实践的转化，同时推动对临床相关问题的进一步研究。该杂志不仅面向医学遗传学家和基础生物医学研究人员，也欢迎处理遗传综合征的临床医生投稿。期刊拥有来自三大洲的四位副主编和一个广泛的国际编辑委员会，欢迎来自全球的最新研究投稿。

Molecular Syndromology

Introduction: Chromosomal microarray analysis (CMA) allows the detection of submicroscopic chromosomal abnormalities. In recent years, its use in prenatal diagnosis has been implemented when certain ultrasound findings are detected. The purpose of this study was to analyze and describe the imbalances detected in prenatal samples collected from pregnancies followed in our center for having the indication to perform diagnosis using CMA. Material and methods: CMA performed in our center on chorionic villi and amniotic fluids during the period 2019-2023 were collected. The inclusion criteria were: normal screening of common aneuploidies and at least one of the following features: nuchal translucency higher than percentile 99, fetal abnormalities, early-onset fetal growth restriction, parents´ history of chromosomal imbalances, or cases with abnormal karyotype. When a relevant variant was detected, it was analyzed in the parents' fetus and when available, the phenotype of the children borned was collected. Results: 216 CMA studies were performed in four years. Pathogenic copy number variations (CNVs) were detected in 13 samples (6%), identifying two concurrent pathogenic alterations in one case. Isolated CNVs had OMIM numbers and corresponded to already reported syndromes. Seven variants of unknown significance (3.7%) were observed. The study of the parents showed that the majority of the variants identified had been produced de novo, except one pathogenic and five unknown CNVs that had been inherited from an apparently healthy parent. Three microduplications drew specially our attention: duplication 5q35.2 which encompassed MSX2 gene (because the reported phenotype is not consistent with what is expected for the genomic region) and duplications 1q21.1 and 16p11.2 (due to the ultrasound findings detected in fetuses had recently been postulated to be associated with these CNVs). Conclusion: The phenotype of CNVs identified in prenatal samples is highly variable prenatally, like postnatally. Some findings may be part of the syndromes to which they give rise and some phenotypes may be pending to define. Further studies are needed to better define these variants and to understand how haploinsufficiency or over-expression of genes included in these regions can cause such complex phenotypes.

Pilar Carrasco Salas

Reyes Granell Escobar

Ana Serrano Mira

Angustias Pérez Saldaña

Marta Cosculluela Vidal

Carlos Garrido

Ignacio Vázquez Rico

Findings in chromosomal microarray analysis during prenatal diagnosis in high-risk individuals

高风险个体产前诊断中染色体微阵列分析的发现

Background: Joubert syndrome type 33 (JBTS33) is a rare autosomal recessive disorder characterized by developmental delay, severe renal disease, hypotonia/ataxia, cerebellar vermian hypoplasia/aplasia, optic nerve atrophy, renal atrophy, and the "molar tooth sign" on imaging. Nearly 40 genes associated with Joubert syndrome have been identified, including CEP290, TMEM216, TMEM67, AHI1, and CC2D2A. Methods: We report a consanguineous family with JBTS33 diagnosed through whole-exome sequencing. A novel biallelic homozygous nonsense mutation (ENST00000326291.11: c.1231C&gt;T; p. Arg411Ter) in PIBF1, Progesterone-Induced Blocking Factor 1, was identified. Results: Our study included three patients with the same homozygous mutation in PIBF1, which contributed to clinical features such as psychomotor issues, dysmorphic features, hypotonia/ataxia, kidney failure, and possibly seizures. All three patients seizures have been eliminated after phenobarbital administration. This mutation has not been reported in public databases. Conclusion: This study confirmed PIBF1 as a disease-causing gene for JBTS33, expanding the molecular and clinical spectrum of JBTS. Our findings underscore the importance of identifying the genetic underpinnings and phenotypic expansions of PIBF1 mutations. Enhanced diagnostic awareness can facilitate early intervention and management. Further research is required to elucidate the relationship between PIBF1 mutations and associated clinical manifestations. Keywords: Joubert Syndrome, PIBF1, Developmental Delay, Renal Cystic Dysplasia, Retinal, Molar tooth sign, WES.

Busra Aynekin

Bahadır M. Samur

Ummu Gulsum Ozgul Gumus

Kaya Bilguvar

Ayten Gulec

Stephanie Efthymiou

Hakan Gumus

Ahmet Okay Caglayan

Huseyin Per

Novel PIBF1 Pathogenic Variant in Three Siblings with Joubert Syndrome Type 33

三例Joubert综合征33型患者中的新型PIBF1致病变异

Introduction: Spondyloepiphyseal dysplasia tarda (SEDT) is an inherited disorder that is typically diagnosed in childhood or adolescence. It is characterized by disproportionate short stature and premature osteoarthritis, and it frequently affects males. Here, we described a novel nonsense mutation, c.406A&gt;T; p(Lys136Ter), in TRAPPC2 (NM_001011658.4) in a Turkish patient with X-linked SEDT. Case Presentation: A 15-year-old boy, born to non-consanguineous Turkish parents, exhibited a decline in height velocity over three years and complained of back pain despite minimal physical activity. Growth and development were normal until adolescence, with the patient's weight at 35 kg (SDS -3.85), height at 134 cm (SDS -5.44), and a predicted adult height of 137.6 cm. Dysmorphic facial features, microtia, synophrys, hypotelorism, and barrel chest were noted. Radiological examination revealed osteopenic bone structure, hypoplastic odontoid process, platyspondyly, scoliosis, short femoral necks, and coxa vara. Genetic analysis identified a hemizygous novel stop codon mutation (c.406A&gt;T; pLys136Ter) in TRAPPC2, also detected as heterozygous in the patient's mother. Conclusion: In adolescence or childhood, X-linked SEDT should be considered in cases of disproportionate short stature, short trunk, osteoarthritis, and a family history that is appropriate for X-linked inheritance. Skeletal survey should be performed to suspect to SEDT and radiological findings may be supported to diagnosis.

Deniz Yasar

Naz Güleray Lafcı

Gülin Karacan Küçükali

Aslıhan Araslı Yılmaz

Beyhan Özkaya Dönmez

Burak Tahir Yazar

Berna Uçan

İclal Okur

Behiye Sarıkaya Özdemir

Erdal Kurnaz

Meliksah Keskin

Şenay Savaş Erdeve

A Novel Premature Termination Codon Mutation in TRAPPC2 is associated with X-linked Spondyloepiphyseal Dysplasia Tarda

TRAPPC2中一种新的提前终止密码子突变与X连锁迟发性脊柱干骺端发育不良相关

Backround: HERC2 encodes an E3 ubiquitin ligase that plays a critical role in brain development. Loss-of-function variants are associated with severe neurodevelopmental phenotypes, including intellectual disability, epilepsy, and various structural anomalies. This report aims to expand phenotypic spectrum of HERC2-related disorders, including an unusual cardiac manifestation. Case Presentation: The proband, a male infant born to consanguineous parents, presented with myoclonia-like eyelid movements at 50 days old and subsequently developed severe neuromotor regression and choreoathetotic movements. Brain MRI revealed diffuse cerebral atrophy, corpus callosum thinning, and bilateral pachygyria. He also exhibited distinct dysmorphic features and dilated cardiomyopathy, confirmed by echocardiography. His sibling presented with similar features, including severe developmental delay and dilated cardiomyopathy. Whole-exome sequencing identified a homozygous likely pathogenic c.7645C&gt;T (p.Gln2549Ter) variant in HERC2 gene. This case report is significant as it describes dilated cardiomyopathy in MRT38, a manifestation not previously associated with HERC2 variants. The unusual cardiac phenotype suggests a potential link between HERC2 dysfunction and mitochondrial impairment, contributing to cardiomyopathy. Conclusion: These patients underscore the importance of recognizing novel clinical features associated with the HERC2 LoF variants, which can guide in disease characterization and patient management.

Hüseyin Bahadır Şenol

Çağatay Günay

Ayşe İpek Polat

Adem Aydın

Ayşe Semra Hiz

Uluç Yiş

A Novel HERC2 Variant in Two Siblings with Autosomal Recessive Intellectual Developmental Disorder-38 and Cardiomyopathy

两个同胞中与常染色体隐性智力发育障碍-38和心肌病相关的HERC2新变异

Introduction: Pontocerebellar hypoplasia (PCH) represents a group of rare disorders with prenatal onset and time-dependent loss of brain parenchyma, predominantly affecting the cerebellum and pons with variable involvement of supratentorial structures. Radiologically and pathologically, they are characterized by small cerebellum and pons. Our study aimed to screen for the TSEN54 gene variants in Egyptian patients with PCH for proper counseling and to describe the brain MRI and the clinical phenotype and compare, them to those described in the literature. Methods: Thirty patients from thirty Egyptian families with a diagnosis of PCH based on neuroimaging findings were selected. Clinical evaluation, radiological findings, and genetic investigations were done for all patients. Results: The common missense variant c.919G&gt;T (p.A307S) was identified in only 6 patients from six unrelated families (6/30; 20%) who showed different degrees of pontocerebellar malformations on brain imaging. Conclusion: The presence of a dragonfly/butterfly-like pattern in the coronal section of the cerebellum recommends genetic testing of TSEN54 as a first step. For negative cases, whole-exome sequencing is essential to reach a definite diagnosis and determine the etiology.

Bayoumi A. Emam

Mohamed S. Abdel-Hamid

Maha Eid

Marian Girgis

Omar A. Ragab

Maha S. Zaki

Hassan El-Kiki

Sawsan Abdel-Hady

Ghada M.H. Abdel-Salam

Screening for TSEN54 Variants in Egyptian Patients with Pontocerebellar Malformations

埃及Pontocerebellar畸形患者中TSEN54变异的筛查

Introduction: The incidence of depression in adolescents is increasing and is associated with severe cognitive impairment. This paper aimed to investigate the relationship between polymorphisms in microRNA-146a-5p (miR-146a-5p) and cognitive impairment in adolescent depression patients. Methods: Quantitative real-time polymerase chain reaction was used to quantify miR-146a-5p in serum. Detection of miR-146a-5p gene polymorphism was performed by TaqMan SNP Genotyping Assay. Odds ratios and 95% confidence intervals (CIs) were calculated by chi-square test (χ2) and logistic regression analysis. Results: Genotyping of miR-146a rs2910164 showed that CC (OR = 0.443, 95% CI, 0.264–0.741, p = 0.002) and GC (OR = 0.445, 95% CI, 0.279–0.712, p = 0.001) genotype reduced the risk of cognitive impairment in adolescent depression. The C allele (OR = 0.794, 95% CI, 0.694–0.741, p = 0.001) was a protective factor for cognitive impairment in adolescent depression compared to the rs2910164 G allele. Rs2910164 (OR = 0.425, 95% CI = 0.273–0.662, p = 0.000) showed a negative correlation with adolescents with cognitive impairment in depression by logistic regression analysis. The level of miR-146a-5p was decreased in carriers of the CC and CG genotypes. Conclusion: Rs2910164 C allele carriers have a low risk of cognitive impairment in adolescent depression and could reduce miR-146a-5p level.

Chunping Xie

Qingting Hu

Chunhu Zhang

Kuancai Deng

Association of MicroRNA-146a-5p Polymorphism with Cognitive Impairment in Adolescents with Depressive Disorder

微小RNA-146a-5p多态性与青少年抑郁症患者认知功能障碍的关联

Abbreviation	Mol. Syndromol.
Journal Impact	0.70
Quartiles(Global)	GENETICS & HEREDITY(Q4)

ISSN	1661-8769, 1661-8777
h-index	42

Publication Information	Publisher: S. Karger AG，Publishing cycle: ，Journal Type: journal，Open Access Journals: No
Basic data	Year of publication: 2010，Proportion of original research papers: 81.82%，Self Citation Rate:0.00%， Gold OA Rate: 8.00%

Molecular Syndromology

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Findings in chromosomal microarray analysis during prenatal diagnosis in high-risk individuals

Novel PIBF1 Pathogenic Variant in Three Siblings with Joubert Syndrome Type 33

A Novel Premature Termination Codon Mutation in TRAPPC2 is associated with X-linked Spondyloepiphyseal Dysplasia Tarda

A Novel HERC2 Variant in Two Siblings with Autosomal Recessive Intellectual Developmental Disorder-38 and Cardiomyopathy

Screening for TSEN54 Variants in Egyptian Patients with Pontocerebellar Malformations

Novel PIBF1 Pathogenic Variant in Three Siblings with Joubert Syndrome Type 33

Findings in chromosomal microarray analysis during prenatal diagnosis in high-risk individuals

A Novel HERC2 Variant in Two Siblings with Autosomal Recessive Intellectual Developmental Disorder-38 and Cardiomyopathy

A Novel Premature Termination Codon Mutation in TRAPPC2 is associated with X-linked Spondyloepiphyseal Dysplasia Tarda

Association of MicroRNA-146a-5p Polymorphism with Cognitive Impairment in Adolescents with Depressive Disorder