scholarly journals Case Report: Second Report of Joubert Syndrome Caused by Biallelic Variants in IFT74

2021 ◽  
Vol 12 ◽  
Author(s):  
Ke Zhongling ◽  
Li Guoming ◽  
Chen Yanhui ◽  
Chen Xiaoru
Keyword(s):  
Developmental Delay ◽  
Joubert Syndrome ◽  
Upper Lip ◽  
New Mutation ◽  
Nasal Bridge ◽  
Whole Exome ◽  
Flat Nasal Bridge ◽  
Development Delay ◽  
A Minor ◽  
Gene Panels

Joubert syndrome (JBTS) is a rare ciliopathy characterized by developmental delay, hypotonia, and distinctive cerebellar and brain stem malformation called the molar tooth sign (MTS). We reported a 15-month-old female with dysmorphic features (flat nasal bridge, almond-shaped eye, and a minor midline notch in the upper lips), hypotonia, polydactyly, development delay, and MTS. Whole exome sequencing revealed biallelic heterozygous mutations c.535C>G(p.Q179E/c.853G>T) (p.E285*) in IFT74, which were inherited from the parents. So far, only one article reported JBTS associated with IFT74 gene mutation, and this is the second report of the fifth patient with JBTS due to variants in IFT74. All five patients had developmental delay, postaxial polydactyly, subtle cleft of the upper lip, hypotonia, and MTS, but notably without renal and retinal anomalies or significant obesity, and they shared the same mutation c.535C>G(p.Q179E) in IFT74, and c.853G>T(p.E285*) that we found was a new mutation in IFT74 that related with Joubert syndrome. Those findings highlight the need for the inclusion of IFT74 in gene panels for JBST testing.

scholarly journals Identification of a novel KAT6A variant in an infant presenting with facial dysmorphism and developmental delay: a case report and literature review

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Soyoung Bae ◽  
Aram Yang ◽  
Jinsup Kim ◽  
Hyun Ju Lee ◽  
Hyun Kyung Park
Keyword(s):  
Developmental Delay ◽  
Congenital Abnormalities ◽  
Genetic Disorder ◽  
Facial Dysmorphism ◽  
Nasal Bridge ◽  
Case Presentation ◽  
Whole Exome ◽  
Gastrointestinal Problems ◽  
Expressive Language Delay ◽  
Serial Assessments

Abstract Background Arboleda-Tham syndrome (ARTHS), caused by a pathogenic variant of KAT6A, is an autosomal dominant inherited genetic disorder characterized by various degrees of developmental delay, dysmorphic facial appearance, cardiac anomalies, and gastrointestinal problems. Case presentation A baby presented multiple facial deformities including a high arched and cleft palate, with philtral ridge and vermilion indentation, a prominent nasal bridge, a thin upper lip, low-set ears, an epicanthal fold, and cardiac malformations. Whole exome sequencing (WES) revealed a heterozygous nonsense mutation in exon 8 of the KAT6A gene (c.1312C>T, p.[Arg438*]) at 2 months of age. After a diagnosis of ARTHS, an expressive language delay was observed during serial assessments of developmental milestones. Conclusions In this study, we describe a case with a novel KAT6A variant first identified in Korea. This case broadens the scope of clinical features of ARTHS and emphasizes that WES is necessary for early diagnosis in patients with dysmorphic facial appearances, developmental delay, and other congenital abnormalities.

scholarly journals A Novel de novo Mutation in EBF3 Associated With Hypotonia, Ataxia, and Delayed Development Syndrome in a Chinese Boy

2021 ◽  
Vol 12 ◽  
Author(s):  
Yanru Huang ◽  
Libin Mei ◽  
Yangdan Wang ◽  
Huiming Ye ◽  
Xiaomin Ma ◽  
...  
Keyword(s):  
Developmental Delay ◽  
Clinical Diagnosis ◽  
De Novo ◽  
Pathogenic Mutation ◽  
De Novo Mutation ◽  
Luciferase Reporter ◽  
Global Developmental Delay ◽  
Whole Exome ◽  
Development Delay ◽  
Delayed Development

ObjectiveGlobal developmental delay has markedly high phenotypic and genetic heterogeneity, and is a great challenge for clinical diagnosis. Hypotonia, ataxia, and delayed development syndrome (HADDS), first reported in 2017, is one type of global development delay. The aim of the present study was to investigate the genetic etiology of a Chinese boy with global developmental delay.MethodsWe combined clinical and imaging phenotyping with trio whole-exome sequencing and Sanger sequencing to the patient and his clinically unaffected parents. A luciferase reporter and immunofluorescence were performed to detect the effect of mutation on transcriptional activity and subcellular localization.ResultsThe patient presented with several previously unreported symptoms in the patients with HADDS, including hemangiomas, mild hearing abnormalities and tracheomalacia. A novel EBF3 c.589A > G missense mutation (p.Asn197Asp, p.N197D) was identified in the patient but not in his parents. By constructing the plasmid and transfecting HEK293T cells, EBF3-N197D mutant showed impaired activation of luciferase reporter expression of the p21 promoter, and the mutant affected its entry into the nucleus.ConclusionTo the best of our knowledge, this is the first report of EBF3 pathogenic mutation which associated with HADDS in the Chinese population. Our results expand the phenotypes and pathogenic mutation spectrum of HADDS, thus potentially facilitating the clinical diagnosis and genetic counseling of HADDS patients.

scholarly journals Challenges and Controversies in the Genetic Diagnosis of Hereditary Spastic Paraplegia

2021 ◽  
Vol 21 (4) ◽  
Author(s):  
Lydia Saputra ◽  
Kishore Raj Kumar
Keyword(s):  
Genetic Diagnosis ◽  
Spastic Paraplegia ◽  
Limb Weakness ◽  
Hereditary Spastic Paraplegias ◽  
Gene Testing ◽  
Testing Strategies ◽  
Whole Exome ◽  
The Right ◽  
Gene Panels ◽  
High Degree

Abstract Purpose of Review The hereditary spastic paraplegias (HSPs) are a group of disorders characterised by progressive lower limb weakness and spasticity. We address the challenges and controversies involved in the genetic diagnosis of HSP. Recent Findings There is a large and rapidly expanding list of genes implicated in HSP, making it difficult to keep gene testing panels updated. There is also a high degree of phenotypic overlap between HSP and other disorders, leading to problems in choosing the right panel to analyse. We discuss genetic testing strategies for overcoming these diagnostic hurdles, including the use of targeted sequencing gene panels, whole-exome sequencing and whole-genome sequencing. Personalised treatments for HSP are on the horizon, and a genetic diagnosis may hold the key to access these treatments. Summary Developing strategies to overcome the challenges and controversies in HSP may hold the key to a rapid and accurate genetic diagnosis.

scholarly journals Whole-exome sequencing in an individual with severe global developmental delay and intractable epilepsy identifies a novel, de novoGRIN2Amutation

Epilepsia ◽  
2014 ◽  
Vol 55 (7) ◽  
pp. e75-e79 ◽  
Author(s):  
Sunita Venkateswaran ◽  
Ken A. Myers ◽  
Amanda C. Smith ◽  
Chandree L. Beaulieu ◽  
Jeremy A. Schwartzentruber ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Developmental Delay ◽  
Whole Exome Sequencing ◽  
Intractable Epilepsy ◽  
Global Developmental Delay ◽  
Whole Exome

scholarly journals Global developmental delay and postnatal microcephaly: Bainbridge-Ropers syndrome with a new mutation in ASXL3

2018 ◽  
Vol 33 (7) ◽  
pp. 484-486
Author(s):  
S.N. Contreras-Capetillo ◽  
Z.H. Vilchis-Zapata ◽  
J. Ribbón-Conde ◽  
D. Pinto-Escalante
Keyword(s):  
Developmental Delay ◽  
Global Developmental Delay ◽  
New Mutation

Whole-exome sequencing identify a new mutation of MYH7 in a Chinese family with left ventricular noncompaction

Gene ◽  
2015 ◽  
Vol 558 (1) ◽  
pp. 138-142 ◽  
Author(s):  
Jing Yang ◽  
Meng Zhu ◽  
Yao Wang ◽  
Xiaofeng Hou ◽  
Hongping Wu ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Left Ventricular ◽  
Chinese Family ◽  
Left Ventricular Noncompaction ◽  
New Mutation ◽  
Ventricular Noncompaction ◽  
Whole Exome

Get Your Molar Tooth Right: Joubert Syndrome Misdiagnosis Unmasked by Whole-Exome Sequencing

2021 ◽  
Author(s):  
Fulvio D’Abrusco ◽  
Filippo Arrigoni ◽  
Valentina Serpieri ◽  
Romina Romaniello ◽  
Caterina Caputi ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Joubert Syndrome ◽  
Molar Tooth ◽  
Whole Exome

Cost Effectiveness of Whole Exome Sequencing for Children with Developmental Delay in a Developing Country: A Study from Jordan

2021 ◽  
Author(s):  
Amira Masri ◽  
Hanan Hamamy
Keyword(s):  
Cost Effectiveness ◽  
Exome Sequencing ◽  
Developmental Delay ◽  
Developing Country ◽  
Whole Exome Sequencing ◽  
Financial Burden ◽  
Indirect Costs ◽  
Cost Effective ◽  
Whole Exome ◽  
The Cost

AbstractThis retrospective study was aiming to determine the cost effectiveness of whole exome sequencing (WES) in the diagnosis of children with developmental delay in a developing country. In this study of 40 patients, the average cost of traditional investigations and indirect costs related to rehabilitation and medications per child were USD847 and 6,585 per year, respectively. With a current cost for WES of approximately USD1,200, we concluded that performing WES could be cost effective, even in countries with limited resources, as it provides the option for genetic counseling in affected families with an ultimate reduction of overall financial burden to both parents and health care system.

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