scholarly journals Evaluation of Sporadic and Familial Cases with Craniofrontonasal Syndrome: A Wide Clinical Spectrum and Identification of a Novel EFNB1 Gene Mutation

2021 ◽  
pp. 1-10
Author(s):  
Semra Gürsoy ◽  
Filiz Hazan ◽  
Tülay Öztürk ◽  
Rüya Çolak ◽  
Şebnem Çalkavur
Keyword(s):  
Gene Mutation ◽  
Genetic Disorder ◽  
Sporadic Case ◽  
Peripheral Blood Lymphocytes ◽  
Clinical Spectrum ◽  
Facial Features ◽  
Phenotype Correlation ◽  
Familial Cases ◽  
Sporadic Cases ◽  
Coronal Synostosis

Craniofrontonasal syndrome (CFNS) is a rare X-linked genetic disorder which is characterized by coronal synostosis, widely spaced eyes, a central nasal groove, and various skeletal anomalies. Mutations in the <i>EFNB1</i> gene in Xq13.1 are responsible for familial and sporadic cases. In the present study, we aimed to evaluate the clinical characteristics and molecular results of 4 patients with CFNS. Genomic DNA was extracted from the peripheral blood lymphocytes of all patients and their parents, and Sanger sequencing of the <i>EFNB1</i> gene was performed. A novel <i>EFNB1</i> gene mutation (c.65delG; p.Cys22SerfsTer24) was detected in a newborn who had only dysmorphic facial features and bicornuate uterus. The other 3 patients (2 familial cases and 1 sporadic case) shared the same mutation (c.196C&#x3e;T; p.R66X). However, the clinical features of these patients were highly variable. Additionally, central (meso-axial) polydactyly and deep palmar creases were detected, which have not been previously reported. CFNS has a wide clinical spectrum, but there is no clear genotype-phenotype correlation. However, central (meso-axial) polydactyly and deep palmar creases may be part of the clinical spectrum seen in CFNS. In addition, our findings expand the mutational spectrum in patients with CFNS.

Molecular Screening of MKRN3, DLK1, and KCNK9 Genes in Girls with Idiopathic Central Precocious Puberty

2017 ◽  
Vol 88 (3-4) ◽  
pp. 194-200 ◽  
Author(s):  
Anna Grandone ◽  
Carlo Capristo ◽  
Grazia Cirillo ◽  
Marcella Sasso ◽  
Giuseppina Rosaria Umano ◽  
...  
Keyword(s):  
Precocious Puberty ◽  
Rare Variants ◽  
Point Mutations ◽  
Central Precocious Puberty ◽  
Sporadic Case ◽  
Age At Menarche ◽  
Nucleotide Polymorphisms ◽  
Familial Cases ◽  
Idiopathic Central Precocious Puberty ◽  
Sporadic Cases

Background: Mutations in the imprinted gene MKRN3 have been described as a common genetic cause of idiopathic central precocious puberty (CPP), in particular in familial cases. However, the exact prevalence of mutations is unknown. Single nucleotide polymorphisms in 2 other imprinted genes, DLK1 and KCNK9, have been associated with age at menarche. We investigated the prevalence of mutations in MKRN3, DLK1, and KCNK9 genes in a cohort of girls with idiopathic CPP. Methods: MKRN3, DLK1, and KCNK9 coding regions were sequenced in 60 girls with idiopathic CPP (familial in 23 cases). Results: Three mutations, including a new one, in MKRN3 were found in 2 familial cases (c.1229G>A; p.Cys410Ter and c.477_485del; p.Pro160Cysfs*14) (8.7%) and in 1 sporadic case (c.982C>T; p.Arg328Cys) (2.8%). We did not find rare variants in DLK1 and KCNK9 genes. Conclusions: (1) The prevalence of MKRN3 mutations in our cohort was similar to that reported in the literature in sporadic cases but lower than previously described in familial ones. This could be due to different inheritance patterns of families studied; (2) we expanded the phenotype of MKRN3 defects describing 3 more patients with MKRN3 mutations; and (3) point mutations in DLK1 and KCNK9 at least do not seem to be a common cause of CPP in girls.

A Family with Craniofrontonasal Syndrome

2018 ◽  
Vol 55 (7) ◽  
pp. 1026-1029 ◽  
Author(s):  
Yoshikazu Inoue ◽  
Yoshiaki Sakamoto ◽  
Masanori Sugimoto ◽  
Hidehito Inagaki ◽  
Hiroko Boda ◽  
...  
Keyword(s):  
Tyrosine Kinases ◽  
Cleft Lip ◽  
Cleft Lip And Palate ◽  
Genetic Disorder ◽  
Japanese Family ◽  
Eph Receptor ◽  
Familial Cases ◽  
Bilateral Cleft Lip ◽  
Coronal Synostosis ◽  
The Common

Craniofrontonasal syndrome (CFNS) is a very rare genetic disorder, the common physical malformations of which include coronal synostosis, widely spaced eyes, clefting of the nasal tip, and various skeletal anomalies. Mutations of EFNB1, which encodes a member of the ephrin family of transmembrane ligands for Eph receptor tyrosine kinases, is the cause of CFNS. Although familial CFNS cases have been reported, no studies in the literature describe familial cases of CFNS expressing bilateral cleft lip and palate. Here, we describe a Japanese family with three cases of CFNS expressing bilateral cleft lip and palate.

Association of apolipoprotein E and myeloperoxidase genotypes to clinical course of familial and sporadic multiple sclerosis

2004 ◽  
Vol 10 (3) ◽  
pp. 266-271 ◽  
Author(s):  
B Zakrzewska-Pniewska ◽  
M Styczynska ◽  
A Podlecka ◽  
R Samocka ◽  
B Peplonska ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Apolipoprotein E ◽  
Brain Atrophy ◽  
Genetic Factors ◽  
Clinical Course ◽  
Progression Rate ◽  
Disease Course ◽  
Familial Cases ◽  
Sporadic Cases ◽  
The Relationship

The importance of apolipoprotein E (ApoE) and myeloperoxidase (MPO) genotypes in the clinical characteristics of multiple sclerosis (MS) has been recently emphasized. In a large group of Polish patients we have tested the hypothesis that polymorphism in ApoE and MPO genes may influence the course of the disease. G enotypes were determined in 117 MS patients (74 females and 43 males; 99 sporadic and 18 familial cases) with mean EDSS of 3.6, mean age of 44.1 years, mean duration of the disease 12.8 years and mean onset of MS at 31.2 years, and in 100 healthy controls. The relationship between ApoE and MPO genes’ polymorphism and the MS activity as well as the defect of remyelination (diffuse demyelination) and brain atrophy on MRI were analysed. The ApoE o4 allele was not related to the disease course or the ApoE o2 to the intensity of demyelination on MRI. The genotype MPO G/G was found in all familial MS and in 57% (56/99) of sporadic cases. This genotype was also related to more pronounced brain atrophy on MRI. The MPO G/G subpopulation was characterized by a significantly higher proportion of patients with secondary progressive MS (PB- 0.05) and by a higher value of EDSS. A ccording to our results the MPO G allele is frequently found (in 96% of cases) among Polish patients with MS. More severe nervous tissue damage in the MPO G/G form can be explained by the mechanism of accelerated oxidative stress. It seems that MPO G/G genotype may be one of the genetic factors influencing the progression rate of disability in MS patients.

MG-106 Global developmental delay and characteristic facial features associated with pacs1 gene mutation – report of two cases

2015 ◽  
Vol 52 (Suppl 1) ◽  
pp. A1.2-A1
Author(s):  
Lauren Chad ◽  
Brian HY Chung ◽  
Christian R Marshall ◽  
Daniele Merico ◽  
Riyana Babul-Hirji ◽  
...  
Keyword(s):  
Developmental Delay ◽  
Gene Mutation ◽  
Global Developmental Delay ◽  
Facial Features

scholarly journals Prenatal diagnosis of a 4.5-Mb deletion at chromosome 4q35.1q35.2: Case report and literature review

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Gefei Xiao ◽  
Xianrong Qiu ◽  
Yuqiu Zhou ◽  
Gongjun Tan ◽  
Yao Shen
Keyword(s):  
Single Copy ◽  
Peripheral Blood Lymphocytes ◽  
Chromosomal Microarray ◽  
Congenital Defects ◽  
Banding Technique ◽  
Chromosomal Microarray Analysis ◽  
Phenotype Correlation ◽  
Protein Coding ◽  
Genotype Phenotype Correlation ◽  
Number Variation

Abstract Objective We present a genetic analysis of an asymptomatic family with a 4q terminal deletion; we also review other similar published studies and discuss the genotype–phenotype correlation. Methods A karyotype analysis was performed on the amniotic fluid cells of a woman at 24 weeks of pregnancy and peripheral blood lymphocytes from both parents and their older son with the conventional G-banding technique. Chromosomal microarray analysis (CMA) testing was carried out for both parents and the fetus to analyze copy number variation (CNV) in the whole genome. Results The results showed no abnormalities in the karyotypes of the father and older son, and the karyotypes of the mother and fetus were 46,XX,del(4)(q35.1) and 46,XY,del(4)(q35.1), respectively. CMA results showed a partial deletion at the 4q terminus in both the fetus and mother. The deletion region of the fetus was arr[GRCh37] 4q35.1q35.2(186,431,008_190,957,460) × 1; the loss size of the CNV was approximately 4.5 Mb and involved 14 protein-coding genes, namely, CYP4V2, F11, FAM149A, FAT1, FRG1, FRG2, KLKB1, MTNR1A, PDLIM3, SORBS2, TLR3, TRIML1, TRIML2, and ZFP42. No variation on chromosome 4 was detected in the father’s CMA results. Conclusion Deletion of the 4q subtelomeric region is a familial variation. The arr[GRCh37] 4q35.1q35.2(186,431,008_190,957,460) region single-copy deletion did not cause obvious congenital defects or mental retardation. The application of high-resolution genetic testing technology combined with the analysis of public genetic database information can more clearly elucidate the genotype–phenotype correlation of the disease and provide support for both prenatal and postnatal genetic counseling.

scholarly journals Identification and Functional Characterization of a Novel De Novo RUNX2 Frameshift Mutation Associated With Cleidocranial Dysplasia

2021 ◽  
Author(s):  
Lei Gong ◽  
Bekzod Odilov ◽  
Feng Han ◽  
Fuqiang Liu ◽  
Yujing Sun ◽  
...  
Keyword(s):  
Frameshift Mutation ◽  
De Novo ◽  
Novel Mutation ◽  
Genetic Disorder ◽  
Functional Characterization ◽  
Sporadic Case ◽  
Luciferase Assay ◽  
Cleidocranial Dysplasia ◽  
Wild Type ◽  
Bone And Cartilage Development

Abstract BackgroundCleidocranial dysplasia (CCD) is a rare genetic disorder affecting bone and cartilage development. Clinical features of CCD comprise short stature, delayed ossification of craniofacial structures with numerous Wormian bones, underdeveloped or aplastic clavicles and multiple dental anomalies. Several studies have revealed that CCD development is strongly linked with different mutations in Runt-related Transcription Factor 2 (RUNX2) gene. In this study, we report a case with typical CCD presentations. MethodsWe performed genetic testing of participants and found a novel RUNX2 frameshift mutation: c.1550delT in a sporadic case. We also compared the functional activity of the mutant and wild-type RUNX2 through immunofluorescence microscopy and osteocalcin promoter luciferase assay. ResultsBoth mutant RUNX2 and wild‑type RUNX2 protein were similarly confined in the nuclei. The novel mutation caused abrogative transactivation activity of RUNX2 on osteocalcin promoter. ConclusionsWe explored a novel RUNX2 deletion/frameshift mutation in a sporadic CCD patient. This finding emphasizes on crucial role of VWRPY domain in RUNX2 transactivation ability.

scholarly journals Detection of the CD18 gene mutation as a marker of BLAD genetic disorder of Holstein-Friesian cattle in West Java

2020 ◽  
Vol 18 (2) ◽  
pp. 116
Author(s):  
Mukh Fajar Nasrulloh ◽  
Ari Sulistyo Wulandari ◽  
Indriawati Indriawati ◽  
Endang Tri Margawati ◽  
Slamet Diah Volkandari
Keyword(s):  
Gene Mutation ◽  
Leukocyte Adhesion ◽  
Genetic Disorder ◽  
Rflp Analysis ◽  
West Java ◽  
Holstein Friesian ◽  
Pcr Rflp ◽  
Dairy Cattle Breeding ◽  
Disorder Identification ◽  
Cluster Of Differentiation

<p class="MDPI17abstract"><strong>Objective: </strong>Bovine Leukocyte Adhesion Deficiency (BLAD) is a genetic disorder in Holstein-Friesian (HF) cattle that have a significant economic impact on dairy cattle breeding. Mutation c.383A&gt;G in Cluster of Differentiation Molecule 18 (CD18) gene was known as related to BLAD. This study aimed to detect the CD18 gene mutation that causes BLAD of HF cattle in the West Java Province.</p><p class="MDPI17abstract"><strong>Methods: </strong>The genomic DNA was extracted from 88 blood samples of HF cattle from Cibungbulang-Bogor (n=34), Ciampea-Bogor (n=31), and Sukabumi (n=23) by the GB300 DNA extraction kit, Geneaid<sup>TM</sup>. The CD18 gene mutation was detected by PCR-RFLP analysis using the <em>Taq</em>I restriction endonuclease.<strong></strong></p><p class="MDPI17abstract"><strong>Results: </strong>All samples in this study produced two fragments DNA, i.e., 359 bp and 260 bp with the monomorphic homozygote genotype (BB). HF cattle with BB genotype indicated as normal cattle and did not carry BLAD.<strong></strong></p><strong>Conclusions: </strong>All samples in the three populations of West Java were free of BLAD genetic disorder. Identification of BLAD on HF cattle in other places, including bulls in the Center of Semen Production in Indonesia was needed to prevent this genetic disorder.

scholarly journals Cantu syndrome and hypopituitarism: implications for endocrine monitoring

2019 ◽  
Vol 2019 ◽  
Author(s):  
Nicholas J Theis ◽  
Toby Calvert ◽  
Peter McIntyre ◽  
Stephen P Robertson ◽  
Benjamin J Wheeler
Keyword(s):  
Anterior Pituitary ◽  
Autosomal Dominant ◽  
Genetic Disorder ◽  
Facial Features ◽  
Pituitary Hormone ◽  
List Type ◽  
Pituitary Dysfunction ◽  
Pathogenic Variants ◽  
Clinical Surveillance ◽  
Learning Points

Summary Cantu syndrome, or hypertrichotic osteochondrodysplasia, is a rare, autosomal dominant genetically heterogeneous disorder. It is characterized by hypertrichosis, cardiac and skeletal anomalies and distinctive coarse facial features. We report a case where slowed growth velocity at 13 years led to identification of multiple pituitary hormone deficiencies. This adds to other reports of pituitary abnormalities in this condition and supports inclusion of endocrine monitoring in the clinical surveillance of patients with Cantu syndrome. Learning points: Cantu syndrome is a rare genetic disorder caused by pathogenic variants in the ABCC9 and KCNJ8 genes, which result in gain of function of the SUR2 or Kir6.1 subunits of widely expressed KATP channels. The main manifestations of the syndrome are varied, but most commonly include hypertrichosis, macrosomia, macrocephaly, coarse ‘acromegaloid’ facies, and a range of cardiac defects. Anterior pituitary dysfunction may be implicated in this disorder, and we propose that routine screening should be included in the clinical and biochemical surveillance of patients with Cantu syndrome.

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