Clinical Findings in Four Brazilian Families Affected by Saethre-Chotzen Syndrome without TWIST Mutations

Objective To analyze the dysmorphological variability and to investigate the presence of mutations in the exon 1 of TWIST gene using direct sequencing in Brazilian families presenting with Saethre-Chotzen Syndrome (SCS). Methods Four families with 24 patients diagnosed as having features of SCS were studied. Phenotypic characteristics of all patients were inventoried. The investigation protocol included anamnesis, dysmorphological examination, abdominal ultrasound, spine and cranium x-ray, chromosomal analysis on GTG banding, and screening for mutations in the exon 1 of TWIST gene. Results Frequent facial features included brachycephaly (24 of 24), facial asymmetry (20 of 24), prominent ears crus (15 of 24), low-set ears (14 of 24), maxillary hypoplasia (13 of 24), prominent nasal bridge (13 of 24), ptosis of the eyelids (12 of 24), and low-set frontal hairline (12 of 24). Limb abnormalities such as partial hand cutaneous syndactyly (18 of 24), clinodactyly (13 of 24), and broad great toes (13 of 24), and partial cutaneous syndactyly of the feet (9 of 24) were also detected. Among radiological findings were relevant bicoronal (eight of nine) and unicoronal (one of nine) craniosynostosis, digital impressions (eight of nine), bilateral parietal foramina (two of nine), partial fusion 1 and 2 degrees costal arches (two of nine) and bifid spine on lumbar vertebra (two of nine). GTG-banding chromosomal analyses were normal. No TWIST gene mutations were found. Conclusions Affected individuals in these four SCS families may carry mutations in other genes of the same developmental pathway. Considering the complexity of the genes involved in skull-limbs development, an accurate dysmorphological evaluation in patients with SCS and their families is especially important for genetic counseling.

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Clinical, hormonal, and molecular genetic characteristics of patients with Р450с17 (17a-hydroxylase/17,20-liase) insufficiency

Problems of Endocrinology ◽

10.14341/probl11304 ◽

2001 ◽

Vol 47 (1) ◽

pp. 20-24

Author(s):

A. N. Tyulpakov ◽

N. Yu. Kalinchenko ◽

S. Yu. Kalinchenko ◽

L. Ya. Rozhinskaya ◽

P. M. Platonova ◽

...

Keyword(s):

Differential Diagnosis ◽

Sex Steroids ◽

Direct Sequencing ◽

Molecular Genetic ◽

Corticosterone Level ◽

Clinical Findings ◽

Testicular Feminization ◽

Genetic Characteristics ◽

Exon 1 ◽

Male Karyotype

Deficiency of Р450с17 (17a-hydroxylase/17,20-liase) is а rare hereditary steroidogenesis defects disordering the synthesis of sex steroids and leading to excessive production of mineralocorticoid production. Clinical findings and results of molecular and hormonal studies in 6patients with P450cl7 deficiency are presented. All patients were born with female phenotype, 5 with male karyotype and 1 with female karyotype. Testicular feminization was erroneously diagnosed in all genetic men, and the genetic woman was treated for ovarian in sufficiency. Five of 6 patients suffered from severe arterial hypertension (up to 100/130 mm Hg). Hypopotassemia was observed in 3 patients. P450cl7 deficiency was diagnosed on the basis of increased serum corticosterone level, and in 4 patients it was confirmed by multisteroid analysis. Amplification and subsequent direct sequencing of CYP17gene revealed homozygotic mutation in exon 1 (R96Q) in 1 patient. The same mutations in exon 6 (V360L) were detected in 2 unrelated families (4 patients). Constituent heterozygosis by 2 mutations, in exon 6 (R347C) and exon 8 (R416C), was detected in 1 patient. These findings evidence the need in differential diagnosis of P450cl7 deficiency and the testicular feminization syndrome.

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Gastric antral vascular ectasia in children, rare presentation

BMJ Case Reports ◽

10.1136/bcr-2020-236896 ◽

2020 ◽

Vol 13 (11) ◽

pp. e236896

Author(s):

Matthew Pizzuto ◽

Sarah Ellul ◽

Mohamed Shoukry

Keyword(s):

Gastrointestinal Endoscopy ◽

Abdominal Ultrasound ◽

Clinical Findings ◽

Evidence Based ◽

Gastric Antral Vascular Ectasia ◽

Perianal Area ◽

Rare Presentation ◽

Vascular Ectasia ◽

Blood Tests ◽

Abdominal Examination

A 14-year-old boy, a known case of perinatal hypoxic cerebral palsy, presented to paediatric emergency with acute melaena and blood staining around feeding gastrostomy site. Physical examination revealed pallor, but no signs of distress with an unremarkable abdominal examination. Routine blood tests revealed normochromic. Abdominal ultrasound scan and Meckel’s scan were unremarkable. The patient underwent examination under anaesthesia of the perianal area and joint upper and lower gastrointestinal endoscopy. Streak-like gastritis with no signs of active bleeding lesions were noted and patchy areas of colitis involving the descending and sigmoid colon and the rectum. All clinical findings and evidence-based diagnosis matched gastric antral vascular ectasia. He was successfully managed conservatively with elemental hydrolysed feeding formula.

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X-Linked Hypohidrotic Ectodermal Dysplasia: New Features and a Novel EDA Gene Mutation

Cytogenetic and Genome Research ◽

10.1159/000478922 ◽

2017 ◽

Vol 152 (3) ◽

pp. 111-116 ◽

Cited By ~ 6

Author(s):

Salvatore Savasta ◽

Giorgia Carlone ◽

Riccardo Castagnoli ◽

Francesca Chiappe ◽

Francesco Bassanese ◽

...

Keyword(s):

Gene Mutation ◽

Ectodermal Dysplasia ◽

Novel Mutation ◽

Nucleotide Position ◽

Hypohidrotic Ectodermal Dysplasia ◽

Nasal Bridge ◽

Mutation Database ◽

Exon 1 ◽

Male Karyotype ◽

Eda Gene

We described a 5-year-old male with hypodontia, hypohidrosis, and facial dysmorphisms characterized by a depressed nasal bridge, maxillary hypoplasia, and protuberant lips. Chromosomal analysis revealed a normal 46,XY male karyotype. Due to the presence of clinical features of hypohidrotic ectodermal dysplasia (HED), the EDA gene, located at Xq12q13.1, of the patient and his family was sequenced. Analysis of the proband's sequence revealed a missense mutation (T to A transversion) in hemizygosity state at nucleotide position 158 in exon 1 of the EDA gene, which changes codon 53 from leucine to histidine, while heterozygosity at this position was detected in the slightly affected mother; moreover, this mutation was not found in the publically available Human Gene Mutation Database. To date, our findings indicate that a novel mutation in EDA is associated with X-linked HED, adding it to the repertoire of EDA mutations.

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Clinical manifestations of familial exudative vitreoretinopathy in children with nucleotide sequence alterations in the FZD4 gene

Russian Ophthalmological Journal ◽

10.21516/2072-0076-2021-14-4-52-59 ◽

2021 ◽

Vol 14 (4) ◽

pp. 52-59

Author(s):

L. A. Katargina ◽

V. V. Kadyshev ◽

E. V. Denisova ◽

E. A. Geraskina ◽

A. V. Marakhonov ◽

...

Keyword(s):

Nucleotide Sequence ◽

Direct Sequencing ◽

Molecular Genetic ◽

Clinical Manifestations ◽

Gene Mutations ◽

Interdisciplinary Approach ◽

Ophthalmological Examination ◽

Photographic Recording ◽

Familial Exudative Vitreoretinopathy ◽

National Medical

Familial exudative vitreoretinopathy (FEVR)is a rare genetically heterogeneous disease with multiple types of inheritance (autosomal dominant, autosomal recessive, X-linked) and widely varying clinical features. Up to 40 % of cases of FEVR are associated with mutations of the FZD4 gene.Purpose: to investigate the clinical manifestations of FEVR in children with nucleotide sequence alterations in the FZD4 gene. Material and methods. The Helmholtz National Medical ResearchCenter of Eye Diseases and the ResearchCentre for MedicalGenetics conducted a joint in-depth ophthalmological examination of 18 patients aged from 3 weeks to 17 years with a diagnosis of FEVR, which included a detailed ophthalmoscopy under drug mydriasis, ultrasound and electrophysiological examination, photographic recording of fundus changes using RetCam and Fundus Foto. Molecular genetic examination was carried out by direct sequencing according to Sanger. Results. Nucleotide sequence alterations in the FZD4 gene were detected in 3 patients(16.7 %)from two unrelated families. In one family, a 12-year-old girl wasfound to display the firstsymptoms of ophthalmic pathology (reduced vision, strabismus) at the age of 3.5 years. In another family, the clinical manifestations of FZD4 gene mutations were observed in two children during the first year of life (at the age of 5 and 11 months).Conclusions. The clinical picture of 3 patients with detected changes in the nucleotide sequence of the FZD4 gene is characterized by early manifestation and bilateral asymmetric ophthalmoscopic damage. The results of the study indicate the need for a timely diagnosis of FEVR in young children, recommend an interdisciplinary approach to the study of the disease, which should contribute to a better understanding of pathogenesis, and the development of an effective diagnostic, treatment and rehabilitation algorithm.

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Cystic fibrosis gene mutations and polymorphisms in Saudi men with infertility

Annals of Saudi Medicine ◽

10.5144/0256-4947.2020.321 ◽

2020 ◽

Vol 40 (4) ◽

pp. 321-329

Author(s):

Talal AlMaghamsi ◽

Naeem Iqbal ◽

Nabil Abdullrahman Al-Esaei ◽

Muhsina Mohammed ◽

Kamel Zein Eddin ◽

...

Keyword(s):

Cystic Fibrosis ◽

Sample Size ◽

Conflicts Of Interest ◽

Direct Sequencing ◽

Tertiary Care ◽

Gene Mutations ◽

Small Sample ◽

Cystic Fibrosis Gene ◽

Control Group ◽

Primary Infertility

ABSTRACT BACKGROUND: Some mutations of the cystic fibrosis transmembrane regulator ( CFTR ) gene may impair spermatogenesis or cause a congenital absence of the vas deferens that manifests as isolated male infertility. OBJECTIVE: Assess the frequency and analyze the spectrum of CFTR gene variations in Saudi men with primary infertility. DESIGN: Prospective, cross-sectional. SETTING: Tertiary care specialist hospital in Jeddah. PATIENTS AND METHODS: Genomic DNA was extracted from peripheral blood samples of Saudi men who presented with primary infertility to the outpatient andrology clinic with either azoospermia or oligoasthenoteratozoospermia. Polymerase chain reaction and direct sequencing were used to identify all variants of the CFTR gene. MAIN OUTCOME MEASURES: Proportion of the patients with a mutant CFTR gene and the spectrum of CFTR gene variations. SAMPLE SIZE: 50 infertile Saudi men. RESULTS: This study identified 10 CFTR gene variants in 7 (14%) subjects (100 chromosomes). The detected variants and polymorphisms were: c.1408G>A, c.4389G>A, c.2562T>G, c.869+11C>T, c.2909-92G>A, c.3469-65C>A, c.1210-6delT, c.1210-6T>A, c.2988+1G>A, and c.1210-13GT>TG. CONCLUSION: We demonstrated that 14% of the study subjects had one or more CFTR mutations and these were compounded in most of the affected patients. The spectrum of CFTR gene mutations in these subjects was similar to the mutations reported in other studies throughout the world. LIMITATIONS: Small sample size and the lack of a control group. CONFLICTS OF INTEREST: None.

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Rapid detection of exon 1 NRAS gene mutations using universal heteroduplex generator technology

Human Mutation ◽

10.1002/humu.10160 ◽

2003 ◽

Vol 21 (2) ◽

pp. 132-137 ◽

Cited By ~ 4

Author(s):

Carolina Belli ◽

Carlos De Brasi ◽

Irene Larripa

Keyword(s):

Rapid Detection ◽

Gene Mutations ◽

Exon 1

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Genetic disturbances in patients with bodily isomerism from a single center: clinical implications of affected genes and potential impact of ciliary dyskinesia

Cardiogenetics ◽

10.4081/cardiogenetics.2016.5818 ◽

2016 ◽

Vol 6 (1) ◽

Author(s):

Rohit S. Loomba ◽

Peter C. Frommelt ◽

Robert H. Anderson

Keyword(s):

Clinical Course ◽

Gene Mutations ◽

Clinical Findings ◽

Specific Gene ◽

Clinical Implications ◽

Single Center ◽

Clinical Support ◽

Potential Impact ◽

Ciliary Dyskinesia

So-called heterotaxy or isomerism is characterized by abnormal lateralization and malformations of the bodily organs. The mechanism is unclear, although there is growing evidence that ciliary dyskinesia is involved. We reviewed genetic findings from patients with isomerism to determine if affected genes were known to be associated with isomerism and ciliary dyskinesia and determine associations between genotype and clinical findings. We identified patients with isomerism cared for over a 16-year period. Characteristics were compared between those with and without identified mutations. A total of 83 patients with isomerism were identified. Of those who had genotyping, 14/27 had mutations identified, most frequently involving the CFC1 and NODAL genes. Specific mutations were associated with clinical findings, with NODAL mutations often portending need for increased clinical support. Genes associated with isomerism and/or ciliary dyskinesia were identified in the cohort. Specific gene mutations may help predict clinical course.

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Novel ABCD1 gene mutations in Iranian pedigrees with X-linked adrenoleukodystrophy

Journal of Pediatric Endocrinology and Metabolism ◽

10.1515/jpem-2019-0244 ◽

2019 ◽

Vol 32 (11) ◽

pp. 1207-1215

Author(s):

Babak Emamalizadeh ◽

Yousef Daneshmandpour ◽

Abbas Tafakhori ◽

Sakineh Ranji-Burachaloo ◽

Sajad Shafiee ◽

...

Keyword(s):

Protein Structure ◽

Direct Sequencing ◽

Gene Mutations ◽

Protein Product ◽

Structure And Function ◽

Novel Mutations ◽

Chain Reaction ◽

Abcd1 Gene ◽

Polymerase Chain ◽

And Function

Abstract Background X-linked adrenoleukodystrophy (X-ALD), the most common peroxisomal disorder, is caused by mutations in the ABCD1 gene located on Xq28. X-ALD is characterized by a spectrum of different manifestations varying in patients and families. Methods Four pedigrees with X-ALD consisting of patients and healthy members were selected for investigation of ABCD1 gene mutations. The mutation analysis was performed by polymerase chain reaction (PCR) followed by direct sequencing of all exons. The identified mutations were investigated using bioinformatics tools to predict their effects on the protein product and also to compare the mutated sequence with close species. Results One previously known missense mutation (c.1978 C > T) and three novel mutations (c.1797dupT, c.879delC, c.1218 C > G) were identified in the ABCD1 gene, each in one family. Predicting the effects of the mutations on protein structure and function indicated the probable damaging effect for them with significant alterations in the protein structure. We found three novel mutations in the ABCD1 gene with damaging effects on its protein product and responsible for X-ALD.

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Common Genetic Variants of MUTYH are not Associated with Cutaneous Malignant Melanoma: Application of Molecular Screening by Means of High-Resolution Melting Technique in a Pilot Case-Control Study

The International Journal of Biological Markers ◽

10.5301/jbm.2011.6285 ◽

2011 ◽

Vol 26 (1) ◽

pp. 37-42 ◽

Cited By ~ 4

Author(s):

Concetta Santonocito ◽

Andrea Paradisi ◽

Rodolfo Capizzi ◽

Eleonora Torti ◽

Sara Lanza-Silveri ◽

...

Keyword(s):

High Resolution ◽

High Resolution Melting ◽

Direct Sequencing ◽

Strong Association ◽

Laboratory Data ◽

Gene Mutations ◽

Case Control ◽

Common Genetic Variants ◽

Mutyh Gene ◽

Embryonic Origin

MUTYH glycosylase recognizes the 8-oxoG:A mismatch and is able to excise the adenine base using proofreading mechanisms. Some papers have reported a strong association between cancer development or aggressiveness and MUTYH gene mutations. The aim of this study was to find a possible association between the most frequent MUTYH mutations and melanoma in the context of a case-control pilot study. One hundred ninety-five melanoma patients and 195 healthy controls were matched for sex and age. Clinical and laboratory data were collected in a specific database and all individuals were analyzed for MUTYH mutations by high-resolution melting and direct sequencing techniques. Men and women had significantly different distributions of tumor sites and phototypes. No significant associations were observed between the Y165C, G382D and V479F MUTYH mutations and risk of melanoma development or aggressiveness. Our preliminary findings therefore do not confirm a role for MUTYH gene mutations in the melanoma risk. Further studies are necessary for the assessment of MUTYH not only in melanoma but also other cancer types with the same embryonic origin, in the context of larger arrays studies of genes involved in DNA stability or integrity.

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Frequency of AIP Gene Mutations in Young Patients With Acromegaly: A Registry-Based Study

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2014-2094 ◽

2014 ◽

Vol 99 (12) ◽

pp. E2789-E2793 ◽

Cited By ~ 19

Author(s):

Christof Schöfl ◽

Jürgen Honegger ◽

Michael Droste ◽

Martin Grussendorf ◽

Reinhard Finke ◽

...

Keyword(s):

Family History ◽

Direct Sequencing ◽

Positive Family History ◽

Young Patients ◽

Gene Mutations ◽

Interacting Protein ◽

Aryl Hydrocarbon ◽

Number Of Patients ◽

The Individual ◽

Aip Gene

Context: Familial and sporadic GH-secreting pituitary adenomas are associated with mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene. Patients with an AIP mutation (AIPmut) tend to have more aggressive tumors occurring at a younger age. Objective: The objective of the study was to investigate the frequency of AIPmut in patients diagnosed at 30 years of age or younger. Design: The German Acromegaly Registry database (1795 patients in 58 centers) was screened for patients diagnosed with acromegaly at 30 years of age or younger (329 patients). Sixteen centers participated and 91 patients consented to AIPmut analysis. Intervention: DNA was analyzed by direct sequencing and multiplex ligation dependent probe amplification Main outcome Measures: The number of patients with AIPmut was measured. Results: Five patients had either a mutation (c.490C>T, c.844C>T, and c.911G>A, three males) or gross deletions of exons 1 and 2 of the AIP gene (n = 2, one female). The overall frequency of an AIPmut was 5.5%, and 2.3% or 2.4% in patients with an apparently sporadic adenoma or macroadenoma, respectively. By contrast, three of four patients (75%) with a positive family history were tested positive for an AIPmut. Except for a positive family history, there were no significant differences between patients with and without an AIPmut. Conclusions: The frequency of AIPmut in this registry-based cohort of young patients with acromegaly is lower than previously reported. Patients with a positive family history should be tested for an AIPmut, whereas young patients without an apparent family history should be screened, depending on the individual cost to benefit ratio.

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