An Early Presentation of a Genomic Variant of Mucopolysaccharidoses II in a Female Newborn Baby

Mucopolysaccharidoses II is a X-linked genetic disorder caused by the deficiency of lysosomal enzyme Iduronate sulfate sulfatase due to mutations of Iduronate 2-sulfatase (IDS) gene which results in accumulation of intralysosomal glycosaminoglycan. X inactivation and gene alterations are known to cause this entity in a female child. We report an unusual case of missense mutation of IDS gene in heterozygous variant with dominant expression in a female neonate presented in early newborn period with incurable severity. X- linked recessive (heterozygous) missense mutation of Exon 8 in IDS gene confirmed a case of Mucopolysaccharidoses II by Sanger sequencing.

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Laron syndrome – A case Report

JMS SKIMS ◽

10.33883/jms.v20i2.204 ◽

2017 ◽

Vol 20 (2) ◽

pp. 104-106

Author(s):

Javaid Ahmad Bhat ◽

Moomin Hussain Bhat ◽

Hilal Bhat ◽

Mona Sood ◽

Shariq Rashid Masoodi

Keyword(s):

Growth Hormone ◽

Case Report ◽

Hormone Receptor ◽

Growth Hormone Receptor ◽

Genetic Disorder ◽

Female Child ◽

Receptor Signaling ◽

Laron Syndrome ◽

Rare Genetic Disorder ◽

Igf I

Background : Laron & colleagues (1966) reported a rare genetic disorder in Israliei Jewish sublings which was characterized by insensitivity to growth hormone due to abnormality in growth hormone receptor or post receptor signaling pathway.Case Report: We hereby report a case of a 5 year old female child who presented to us with features similar to Laron syndrome. The diagnosis was made & confirmed by various Lab. investigations like low IGF-I levels and managed accordingly. JMS 2017; 20 (2):104-106

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First report of X-linked hypohidrotic ectodermal dysplasia with a hemizygous c.1142G > C in the EDA gene: variant of uncertain significance or new pathogenic variant?

Italian Journal of Pediatrics ◽

10.1186/s13052-021-01078-5 ◽

2021 ◽

Vol 47 (1) ◽

Author(s):

Mario Tumminello ◽

Antonella Gangemi ◽

Federico Matina ◽

Melania Guardino ◽

Bianca Lea Giuffrè ◽

...

Keyword(s):

Ectodermal Dysplasia ◽

Genetic Disorder ◽

Missense Variant ◽

Pathogenic Variant ◽

Hypohidrotic Ectodermal Dysplasia ◽

Variant Of Uncertain Significance ◽

Uncertain Significance ◽

Clinical Potential ◽

Genomic Variant ◽

Eda Gene

Abstract Background Hypohidrotic Ectodermal Dysplasia (HED) is a genetic disorder which affects structures of ectodermal origin. X-linked hypohidrotic ectodermal dysplasia (XLHED) is the most common form of disease. XLHED is characterized by hypotrichosis, hypohydrosis and hypodontia. The cardinal features of classic HED become obvious during childhood. Identification of a hemizygous EDA pathogenic variant in an affected male confirms the diagnosis. Case presentation We report on a male newborn with the main clinical characteristics of the X-linked HED including hypotrichosis, hypodontia and hypohidrosis. Gene panel sequencing identified a new hemizygous missense variant of uncertain significance (VUS) c.1142G > C (p.Gly381Ala) in the EDA gene, located on the X chromosome and inherited from the healthy mother. Conclusion Despite the potential functional impact of VUS remains uncharacterized, our goal is to evaluate the clinical potential consequences of missense VUS on EDA gene. Even if the proband’s phenotype is characteristic for classic HED, further reports of patients with same clinical phenotype and the same genomic variant are needed to consider this novel VUS as responsible for the development of HED.

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Van Buchem Disease: First Case Report from the Indian Subcontinent with an Early Presentation

Journal of Child Science ◽

10.1055/s-0041-1723956 ◽

2021 ◽

Vol 11 (01) ◽

pp. e38-e41

Author(s):

Saurabh Maheshwari ◽

Sonam Yangzom ◽

K. Uday Bhanu ◽

Uddandam Rajesh ◽

Ashok Narayan

Keyword(s):

Western Europe ◽

Indian Subcontinent ◽

Genetic Disorder ◽

Rare Condition ◽

Bone Dysplasia ◽

Feedback Mechanism ◽

Early Presentation ◽

First Case ◽

Cranial Nerve Palsies ◽

Van Buchem Disease

AbstractVan Buchem disease is a rare autosomal recessive genetic disorder that causes a compromised inhibitory feedback mechanism resulting in increased bone formation and overgrowth of the skeleton leading to a variety of neurological symptoms. It has been reported in less than 50 patients most of which were in western Europe. We report the first case of this condition from the Indian subcontinent with an early presentation. This patient presented with a global delay in attaining the developmental milestones and progressive reduction in visual acuity and loss of hearing. He had dysmorphic facies, multiple cranial nerve palsies, and severe visual and auditory deficits. Imaging revealed sclerosing bone dysplasia. This case illustrates the clinical and imaging findings of this rare condition.

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Human oocyte maturation arrest caused by a novel missense mutation in TUBB8

Journal of International Medical Research ◽

10.1177/0300060518778638 ◽

2018 ◽

Vol 46 (9) ◽

pp. 3759-3764 ◽

Cited By ~ 7

Author(s):

Jingjing Xiang ◽

Wei Wang ◽

Chunfeng Qian ◽

Jiangyang Xue ◽

Ting Wang ◽

...

Keyword(s):

Genetic Testing ◽

Missense Mutation ◽

Oocyte Maturation ◽

Clinical Examination ◽

Sanger Sequencing ◽

Mutation Screening ◽

Pcr Amplification ◽

Human Oocyte ◽

Maturation Arrest ◽

Class Viii

Objective To explore the etiology of human oocyte maturation arrest in two infertile Chinese sisters. Methods Clinical examination and genetic testing of all available family members were conducted, and the findings were used to create a pedigree. Mutation screening using PCR amplification and DNA Sanger sequencing of the entire tubulin beta 8 class VIII gene ( TUBB8) including intron–exon boundaries was performed to identify mutations. Results A novel missense TUBB8 mutation (c.1054G > T, p.A352S) in the patient and her elder sister was detected and shown to be associated with oocyte maturation arrest. Conclusion Our findings expand the known mutation spectrum of TUBB8 and provide insights into the etiology of human oocyte maturation arrest.

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SMAD4 Y353C promotes the progression of PDAC

BMC Cancer ◽

10.1186/s12885-019-6251-7 ◽

2019 ◽

Vol 19 (1) ◽

Cited By ~ 2

Author(s):

Zusen Wang ◽

Yongxing Li ◽

Shixiong Zhan ◽

Lu Zhang ◽

Shun Zhang ◽

...

Keyword(s):

Cell Proliferation ◽

Missense Mutation ◽

Sanger Sequencing ◽

Tumour Suppressor Gene ◽

Pancreatic Tissue ◽

Ductal Adenocarcinoma ◽

Migration And Invasion ◽

Sequencing Analysis ◽

Smad4 Expression

Abstract Background SMAD4 is frequently inactivated and associated with a poor prognosis in pancreatic ductal adenocarcinoma (PDAC). Abnormal SMAD4 expression also plays an important role in the malignant progression of PDAC. Methods We investigated SMAD4 status in PDAC by immunohistochemical methods to explore the relationships between SMAD4 expression and clinicopathological features and then detected SMAD4 mutations by Sanger sequencing in 95 patients with PDAC to identify new mutation sites in PDAC. We further evaluated the effects of a missense mutation, Y353C, in the SMAD4 MH2 domain, on cell proliferation and migration in vitro. Results Immunohistochemistry showed that the expression of SMAD4 in PDAC carcinoma tissue was significantly lower than that in normal pancreatic tissue, and negative SMAD4 expression was closely related to tumour diameter, staging, lymph node metastasis and differentiation. Sanger sequencing analysis showed that the rate of SMAD4 mutation was 11.8% in 85 PDAC cases, and the novel SMAD4 Y353C missense mutation identified in this study promoted cell migration and invasion without affecting cell proliferation in vitro. Furthermore, SMAD4 Y353C resulted in reduced expression of E-cadherin and increased expression of Vimentin compared with wild-type SMAD4 overexpression. Conclusion This study supports the key role of SMAD4 as a tumour suppressor gene in PDAC and shows that SMAD4 Y353C is associated with poor progression of PDAC.

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A Case of IFAP Syndrome with Severe Atopic Dermatitis

Case Reports in Medicine ◽

10.1155/2015/450937 ◽

2015 ◽

Vol 2015 ◽

pp. 1-4 ◽

Cited By ~ 3

Author(s):

Catarina Araújo ◽

Miguel Gonçalves-Rocha ◽

Cristina Resende ◽

Ana Paula Vieira ◽

Celeste Brito

Keyword(s):

Missense Mutation ◽

Histopathological Examination ◽

Genetic Disorder ◽

Phenotypic Expression ◽

Regulatory System ◽

Hair Follicles ◽

Skin Permeability ◽

Severe Atopic Dermatitis ◽

Permeability Barrier ◽

First Year Of Life

Introduction.The IFAP syndrome is a rare X-linked genetic disorder characterized by the triad of follicular ichthyosis, atrichia, and photophobia.Case Report.A three-month-old Caucasian, male patient was observed with noncicatricial universal alopecia and persistent eczema from birth. He had dystrophic nails, spiky follicular hyperkeratosis, and photophobia which became apparent at the first year of life. Short stature and psychomotor developmental delay were also noticed. Histopathological examination of skin biopsy on left thigh showed epidermis with irregular acanthosis, lamellar orthokeratotic hyperkeratosis, and hair follicles fulfilled by parakeratotic hyperkeratosis. The chromosomal study showed a karyotype 46, XY. Total IgE was 374 IU/mL. One missense mutation c.1360G>C (p.Ala454Pro) in hemizygosity was detected on theMBTPS2gene thus confirming the diagnosis of IFAP syndrome.Conclusions.We describe a boy with a typical clinical presentation of IFAP syndrome and severe atopic manifestations. A novel missense mutation c.1360G>C (p.Ala454Pro) inMBTPS2gene was observed. The phenotypic expression of disease is quantitatively related to a reduced function of a key cellular regulatory system affecting cholesterol and endoplasmic reticulum homeostasis. It can cause epithelial disturbance with failure in differentiation of epidermal structures and abnormal skin permeability barrier. However, no correlation phenotype/genotype could be established.

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A Challenging Case of Severe Infantile Cholestasis in Alpha-1 Antitrypsin Deficiency

Pediatric and Developmental Pathology ◽

10.1177/1093526616686259 ◽

2017 ◽

Vol 20 (2) ◽

pp. 176-181 ◽

Cited By ~ 1

Author(s):

Zahida Khan ◽

Veena L Venkat ◽

Kyle A Soltys ◽

Donna B Stolz ◽

Sarangarajan Ranganathan

Keyword(s):

Liver Diseases ◽

Unusual Case ◽

Newborn Period ◽

Pediatric Liver Disease ◽

Antitrypsin Deficiency ◽

Alpha 1 Antitrypsin Deficiency ◽

Conjugated Hyperbilirubinemia ◽

Alpha 1 Antitrypsin ◽

Infantile Cholestasis ◽

Metabolic Liver Diseases

Jaundice in the newborn period can be physiologic and is often due to benign causes. Jaundice due to conjugated hyperbilirubinemia extending beyond the second week of life may be an early sign of several cholestatic or metabolic liver diseases, and it requires logical and timely analysis so that specific treatments can be initiated. Alpha-1 antitrypsin deficiency is the most common genetic cause of pediatric liver disease and transplantation, and it must be considered when evaluating cholestatic infants. Here, we present an unusual case of alpha-1 antitrypsin deficiency with severe infantile cholestasis and rapid decompensation in the first 4 months of life, where in-depth but timely diagnosis was crucial for the appropriate intervention to take place.

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Physiotherapy and Rehabilitation in a Child with Joubert Syndrome

Case Reports in Pediatrics ◽

10.1155/2017/8076494 ◽

2017 ◽

Vol 2017 ◽

pp. 1-7

Author(s):

Özge İpek ◽

Özge Akyolcu ◽

Banu Bayar

Keyword(s):

Developmental Delay ◽

Genetic Disorder ◽

Clinical Signs ◽

Functional Independence Measure ◽

Female Child ◽

Joubert Syndrome ◽

Functional Independence ◽

Rehabilitation Program ◽

Reverse Direction ◽

Motor Functioning

Objective. Joubert syndrome (JS) is a rare autosomal recessive genetic disorder characterized by brain malformation, hypotonia, breathing abnormalities, ataxia, oculomotor apraxia, and developmental delay. The purpose of this study was to report the efficiency of the physiotherapy and rehabilitation program in a child with JS. Materials and Methods. Our case is a 19-month-old female child with mild clinical signs of JS. The pretreatment and posttreatment motor functioning level of the case was evaluated through the Gross Motor Function Measure (GMFM), whereas the independence level was evaluated through the Pediatric Functional Independence Measure (WeeFIM). The case was included in the rehabilitation program by the physiotherapist for one hour for five days a week throughout the period of 13 months in accordance with the neurodevelopmental treatment principles. Results. The case was able to turn around from the supine position to the reverse direction by oneself, and she was able to rise on her forearms facedown and was able to sit, crawl, and walk independently. The GMFM score was 210, whereas WeeFIM score was 65. Discussion. In the direction of those findings, in Joubert Syndrome, physiotherapy and rehabilitation can be effective in coping with the symptoms causing developmental delay.

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Widespread co-occurrence of two distantly related mitochondrial genomes in individuals of the leaf beetle Gonioctena intermedia

Biology Letters ◽

10.1098/rsbl.2017.0570 ◽

2017 ◽

Vol 13 (11) ◽

pp. 20170570 ◽

Cited By ~ 6

Author(s):

Chedly Kastally ◽

Patrick Mardulyn

Keyword(s):

Mitochondrial Genome ◽

Sanger Sequencing ◽

Leaf Beetle ◽

Universal Primers ◽

Mitochondrial Genomes ◽

Single Individual ◽

Sequencing Technologies ◽

Pcr Products ◽

Nucleotide Divergence ◽

Genomic Variant

Mitochondrial genome heteroplasmy—the presence of more than one genomic variant in individuals—is considered only occasional in animals, and most often involves molecules differing only by a few recent mutations. Thanks to new sequencing technologies, a large number of DNA fragments from a single individual can now be sequenced and visualized separately, allowing new insights into intra-individual mitochondrial genome variation. Here, we report evidence from both (i) massive parallel sequencing (MPS) of genomic extracts and (ii) Sanger sequencing of PCR products, for the widespread co-occurrence of two distantly related (greater than 1% nucleotide divergence, excluding the control region) mitochondrial genomes in individuals of a natural population of the leaf beetle Gonioctena intermedia . Sanger sequencing of PCR products using universal primers previously failed to identify heteroplasmy in this population. Its occurrence was detected with MPS data and may have important implications for evolutionary studies. It suggests the need to re-evaluate, using MPS techniques, the proportion of animal species displaying heteroplasmy.

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Familial Turner syndrome: the importance of information

Journal of Pediatric Endocrinology and Metabolism ◽

10.1515/jpem-2015-0277 ◽

2016 ◽

Vol 29 (5) ◽

Author(s):

Isabel Periquito ◽

Catarina Carrusca ◽

Joana Morgado ◽

Brígida Robalo ◽

Carla Pereira ◽

...

Keyword(s):

Growth Hormone ◽

Turner Syndrome ◽

Unusual Case ◽

Growth Hormone Treatment ◽

Genetic Disorder ◽

Hormone Treatment ◽

Live Births ◽

Tertiary Center ◽

Common Genetic Disorder

AbstractTurner syndrome is a common genetic disorder with an incidence of 1 in 2500 live births. Spontaneous fertility is rare in such patients and is most likely in women with mosaicism or very distal Xp deletions. The authors report an unusual case of familial Turner syndrome in a woman with mosaicism 45,X/46,Xdel(Xp) karyotype with three documented spontaneous pregnancies, which resulted in two daughters with 46,Xdel(X)(p11.4)mat karyotype and a healthy son. The mother was first diagnosed by the age of 11 and did not receive contraceptive medication, due to information that she would be infertile. Both daughters were referred to an endocrinology unit and are now under growth hormone treatment, and have been growing in the 3rd percentile. This family illustrates the complexity and difficulties in counseling, follow-up and treatment in Turner syndrome, namely referring to a tertiary center, fertility and treatment such as growth hormone and hormonal replacement, due to the heterogeneity of the clinical spectrum.

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