Blended Phenotype of Pelger-Huet Anomaly with Osteochondroma and Autosomal Recessive Deafness with Enlarged Vestibular Aqueduct
We report a case with SNHL, multiple skeletal anomalies including osteochondroma, developmental delay, and PHA. Molecular studies revealed a heterozygous pathogenic variant in theLBR gene and a homozygous likely pathogenic variant in theSLC26A4 gene. Due to these 2 variants, he was diagnosed with PHA and DFNB4 with EVA. If goiter develops, DFNB4 with EVA is named Pendred syndrome (PDS), so the patient will be followed up for this condition, and in the current literature, there is no case with PDS and PHA co-existence either. PHA may be accompanied by multiple skeletal abnormalities. In our case, there is also concomitance ...
Source: Molecular Syndromology - January 12, 2022 Category: Molecular Biology Source Type: research
Comprehensive Genetic Analysis of RASopathy in the Era of Next-Generation Sequencing and Definition of a Novel Likely Pathogenic < b > < i > KRAS < /i > < /b > Variation
Conclusion: AlthoughPTPN11 is the most frequently mutated gene in our patient cohort, as in most previous reports, different mutation distribution among the other genes studied motivates the use of a next-generation sequencing gene panel including the possible responsible genes.Mol Syndromol (Source: Molecular Syndromology)
Source: Molecular Syndromology - January 7, 2022 Category: Molecular Biology Source Type: research
Novel Cranial Imaging Findings and a Splice-Site Variant in a Patient with Tyrosinemia Type III, and a Summary of Published Cases
We report on a 20-month-old patient who was investigated due to developmental delay and dysmorphic features. The girl had a novel splice-site mutation in theHPD gene and ventriculomegaly in cranial imaging, which was not previously associated with tyrosinemia type III. Our patient had mild subjective improvement in social skills and language development after dietary therapy was started and her tyrosine levels decreased. We also summarize clinical, biochemical, and genetic findings of previously published patients with biallelicHPD mutations.Mol Syndromol (Source: Molecular Syndromology)
Source: Molecular Syndromology - January 4, 2022 Category: Molecular Biology Source Type: research
What Can We Learn from the Parents of Children Affected with Mucopolysaccharidosis Type III-A in Israel?
Sanfilippo Syndrome, or mucopolysaccharidosis type III (MPS III), is a group of autosomal-recessive lysosomal storage disorders leading to tissue accumulation of heparan sulfate. MPS III is caused by deficiency in one of 4 enzymes involved in lysosomal degradation of heparan sulfate. Based on the relevant enzyme deficiency, 4 types have been recognized. MPS III constitutes a progressive neurodegenerative and systemic disorder. Parents of children diagnosed with MPS III were interviewed using a retrospective questionnaire based on the known clinical manifestations of MPS III. Eight patients from 4 unrelated families of vari...
Source: Molecular Syndromology - December 15, 2021 Category: Molecular Biology Source Type: research
Clinical Implications of Chromosome 16 Copy Number Variation
Chromosome 16 is one of the gene-rich chromosomes; however, approximately 10% of the chromosome 16 sequence is composed of segmental copies, which renders this chromosome instable and predisposes it to rearrangements via frequent nonallelic homologous recombination. Microarray technologies have enabled the analysis of copy number variations (CNV), which may be associated with the risk of developing complex diseases. Through comparative genomic hybridisation in 1,298 patients, we detected 18 cases with chromosome 16 CNV. We identified 2recurrent CNV regions, including 1 at 16p13.11 in 4 patients and another at 16p11.2 in 7 ...
Source: Molecular Syndromology - December 15, 2021 Category: Molecular Biology Source Type: research
Bi-Allelic c.1746G & #x3e;T; p.Leu582= Variants in < b > < i > TUBGCP4 < /i > < /b > in a Boy with Autism: Clinical Data and Literature Review
Bi-allelic mutations in theTUBGCP4 gene have been recently associated with autosomal recessive microcephaly with chorioretinopathy. However, little is known about the genotype-phenotype characteristics of this disorder. Here, we describe a 5-year-old male patient with autism and a normal occipitofrontal circumference. No retinal abnormalities were observed. Brain MRI revealed the presence of enlarged sheaths of both tortuous optic nerves; both eyes had shorter axial lengths. Whole-exome sequencing in trio revealed synonymousTUBGCP4 variants in homozygous state: c.1746G#x3e;T; p.Leu582=. This synonymous variant has been pre...
Source: Molecular Syndromology - December 2, 2021 Category: Molecular Biology Source Type: research
Aicardi-Gouti ères Syndrome due to a < b > < i > SAMHD1 < /i > < /b > Mutation Presenting with Deep White Matter Cysts
We report on the first Polish patient diagnosed with the Aicardi-Gouti ères syndrome 5 (AGS5). AGS is caused by mutations in one of 9 genes (TREX1,RNASEH2A,RNASEH2B,RNASEH2C,SAMHD1,ADAR,IFIH,LSM11,RNU7-1) which stimulate the type I interferon response. The diagnosis was confirmed by identifying a compound heterozygous mutation p.(Phe165Ser)/p.(Gln235*) in theSAMHD1 gene using whole-exome sequencing. The cystic lesions in the temporal lobes are an uncommon finding in the presented patient carrying aSAMHD1 mutation. Reporting new cases expands the range of phenotypes and plays the crucial role in understanding the AGS patho...
Source: Molecular Syndromology - November 18, 2021 Category: Molecular Biology Source Type: research
< b > < i > KMT2B < /i > < /b > -Related Dystonia: Challenges in Diagnosis and Treatment
In this study, we report the first known Turkish case of a novel nonsense mutation c.2453dupT (p.M818fs*28) in theKMT2B (NM_014727.2) gene diagnosed in a male patient withKMT2B-related dystonia (DYT-KMT2B, DYT-28, Dystonia*-28), which is a complex, childhood-onset, progressive, hereditary dystonia. The patient, who is followed up from 9 to 13 years of age, had dysmorphic features, developmental delay, short stature, and microcephaly, in addition to focal dystonia and hemichorea (in the right and left lower extremities). Generalized dystonia involving bulbar and cervical muscles, in addition to dystonic cramps, myoclonus, a...
Source: Molecular Syndromology - November 17, 2021 Category: Molecular Biology Source Type: research
Genetic Characterization of Hereditary Cancer Syndromes Based on Targeted Next-Generation Sequencing
In this study, hereditary cancer panel harboring cancer-related genes was performed on MiSeq Illumina NGS system from peripheral blood samples. Sequencing files were fed into a cloud-based data analysis pipeline. Reportable variants were classified according to the American College of Medical Genetics and Genomics guidelines. Three hundred five individuals were included in the study. Different pathogenic/likely pathogenic variants were detected in 75 individuals. The majority of these variants were in theMUTYH,BRCA2, andCHEK2 genes. Nine novel pathogenic/likely pathogenic variants were identified inBRCA1,BRCA2,GALNT12,ATM,...
Source: Molecular Syndromology - November 4, 2021 Category: Molecular Biology Source Type: research
Xq21.1q21.31 Duplication in Two Male Siblings
We report 2 malesiblings with maternally inherited duplication of Xq21.1q21.31 who demonstrate a variable phenotype. The proband has Prader Willi-like features such as global developmental delay, autism, obesity, short hands, and small genitalia with a history of food seeking behaviour, while his younger brother has isolated speech delay with some autistic features under evaluation. Both siblings have features such as bitemporal narrowing and small hands. It is therefore likely that the phenotype of duplications in this region is broader than PWS phenocopy, and further cases would be required to elucidate this.Mol Syndromo...
Source: Molecular Syndromology - November 1, 2021 Category: Molecular Biology Source Type: research
Contents, Vol. 12, 2021
Mol Syndromol 2021;12:I –VI (Source: Molecular Syndromology)
Source: Molecular Syndromology - October 29, 2021 Category: Molecular Biology Source Type: research
An Atypical Presentation of Mevalonate Kinase Deficiency in Response to Colchicine Treatment
Mevalonate kinase deficiency (MKD) is a periodic fever syndrome. Nonsteroidal anti-inflammatory drugs, corticosteroids, and anakinra are the most common treatments. However, colchicine is considered insufficient in disease control. In this case report, we present an 8-month-old infant with an atypical presentation of MKD. She had recurrent fever episodes, diarrhea, and lethargy. Elevated mevalonic acid was not detected in the urine. However, the genetic investigation showed a novel pathogenic heterozygous c.925G#x3e;C (p.Gly309Arg) variant and a heterozygous c.1129G#x3e;A (p.Val377Ile) mutation in theMVK gene. The patient ...
Source: Molecular Syndromology - October 25, 2021 Category: Molecular Biology Source Type: research
Association < b > < i > SOD2 < /i > < /b > and < b > < i > PON1 < /i > < /b > Gene Polymorphisms with Polycystic Ovary Syndrome in Saudi Women
In this study, we investigate the associations between superoxide dismutase 2 (SOD2) (rs4880) and paraoxonase 1 (PON1) (rs705379) polymorphisms in PCOS in Saudi women. The study included 99 females with PCOS and 98 healthy women as a control. Single nucleotide polymorphisms (SNPs) of promoter regions were determined using TaqMan genotyping assays. Regarding the polymorphism atSOD2 (rs4880), the CC, CT, and TT genotypes were present at rates of 32, 61, and 7% in PCOS patients, and 47, 43, and 10% in controls, respectively. The frequency of the CT genotype in PCOS patients (0.61) was significantly higher than in controls (0....
Source: Molecular Syndromology - October 22, 2021 Category: Molecular Biology Source Type: research
A Novel < b > < i > ATM < /i > < /b > Gene Mutation Affecting Splicing in an Ataxia-Telangiectasia Patient
Ataxia-telangiectasia (AT) is an autosomal recessive disorder characterized by progressive ataxia, choreoathetosis and immunodeficiency beginning in early childhood. An 8-year-old girl was referred with a diagnosis of AT. She had gait disturbance and dysarthria for 3years. Multiple cutaneous telangiectases were observed on her face, trunk and limbs. Sequence analysis of theATM gene revealed a homozygous c.7308 –15A#x3e;G mutation in IVS49. Human Splicing Finder predicted that the mutation could activate an intronic cryptic acceptor site. We designed primers for amplification of related exons (48–50) from cDNA for evalu...
Source: Molecular Syndromology - October 15, 2021 Category: Molecular Biology Source Type: research
The Methylation Status in the Chromosome 11p15.5 Region and Metabolic Disorders in Children with Syndromic and Nonsyndromic Intrauterine Growth Restriction
This study is aimed to investigate the methylation levels of the chromosome 11p15.5 region and metabolic problems in children with syndromic and nonsyndromic IUGR. Methylation analysis was performed for chromosome 11p15.5 in 49 patients (33 with suspected SRS and 16 nonsyndromic IUGR) with Netchine-Harbison clinical scoring (NHCS); uniparental disomy for chromosomes 6, 7, 14, and 20 was evaluated for those who were negative. LoM of ICR1 was detected in 14 of 33 suspected SRS patients with 3 or more criteria of NHCS, 5 had borderline LoM. Maternal uniparental disomy of the chromosomes 7 and 14 was found in 2 patients. The o...
Source: Molecular Syndromology - October 12, 2021 Category: Molecular Biology Source Type: research
