Molecular Syndromology This is an RSS file. You can use it to subscribe to this data in your favourite RSS reader or to display this data on your own website or blog.

Pure Distal 7q Duplication: Describing a Macrocephalic Neurodevelopmental Syndrome, Case Report and Review of the Literature
Pure distal duplications of 7q have rarely been described in the medical literature. The term pure refers to duplications that occur without an accompanying clinically significant deletion. Pure 7q duplications of various segments have previously been reported in the literature; however, pure distal 7q duplications have only been reported in 21 cases. Twenty of these earlier reports described patients who were identified via karyotype and 1 recently by microarray. Cases have also been reported in genomic databases such as DECIPHER and the University of California Santa Cruz genome browser. We have reviewed 7 additional cas...
Source: Molecular Syndromology - March 29, 2021 Category: Molecular Biology Source Type: research

Nonlethal Raine Syndrome in a Newborn Boy Caused by a Novel FAM20C Variant
Raine syndrome (RS) is a rare genetic disorder characterized by osteosclerotic bone dysplasia caused by a homozygous mutation, compound heterozygous mutation, or microdeletion in theFAM20C gene. In the present study, the MiSeq next-generation sequencing platform was used to perform theFAM20C gene sequence analysis. A novel homozygous variant c.1255T#x3e;C (p.W419R) in theFAM20C gene was diagnosed, and a nonlethal RS phenotype was confirmed, thus contributing to the expansion of the nonlethal RS phenotype. Since there is limited information about rare diseases, we believe that these studies will contribute to the literature...
Source: Molecular Syndromology - March 22, 2021 Category: Molecular Biology Source Type: research

Homozygous Missense Variation in PNPLA8 Causes Prenatal-Onset Severe Neurodegeneration
The patatin-like protein family plays an important role in various biological functions including lipid homeostasis, cellular growth, and signaling. Conserved across species, the patatin domain is shared by all 9 members of the PNPLA family without redundancy in the coding sequences. The defective function ofPNPLA2,PNPLA6, andPNPLA9 are known to cause mitochondrial-related neurodegeneration. Recently,PNPLA8 has been associated with mitochondrial myopathy and poor weight gain with lactic acidosis in 3 unrelated families. Using whole-exome sequencing, we identified a homozygous novel missense variation c.1874A#x3e;G in the p...
Source: Molecular Syndromology - March 19, 2021 Category: Molecular Biology Source Type: research

Genetic Mutations Associated with Pierre Robin Syndrome/Sequence: A Systematic Review
Pierre Robin syndrome/sequence (PRS) is associated with a triad of symptoms that includes micrognathia, cleft palate, and glossoptosis that may lead to respiratory obstruction. The syndrome occurs in 2 forms: nonsyndromic PRS (nsPRS), and PRS associated with other syndromes (sPRS). Studies have shown varying genetic mutations associated with both nsPRS and sPRS. The present systematic review aims to provide a comprehensive collection of published literature reporting genetic mutations in PRS. Web of Science, PubMed, and Scopus were searched using the keywords: “Pierre Robin syndrome/sequence AND gene mutation.” The sea...
Source: Molecular Syndromology - March 18, 2021 Category: Molecular Biology Source Type: research

Potential Pitfalls in Pre-implantation Genetic Diagnosis in a Patient with Tuberous Sclerosis and Isolated Mosaicism for a TSC2 Variant in Renal Tissue
We report a case of TSC diagnosed clinically, requesting genetic counselling regarding reproductive risks. No mutation was identified on initial testing of peripheral blood; however, mosaicism for a likely pathogenic frameshift variant inTSC2 was detected at a level of 15% in renal angiomyolipoma tissue. Despite widespread clinical manifestations of TCS, this variant was not detected in skin fibroblasts or saliva, raising the possibility this is an isolated somatic mutation in renal tissue with the underlying germline mutation not yet identified. This case highlights the difficulties when counselling patients with mosaicis...
Source: Molecular Syndromology - March 9, 2021 Category: Molecular Biology Source Type: research

A Recurrent Variant in POLR1B , c.3007C & #x3e;T; p.Arg1003Cys, Associated with Atresia of the External Canal and Microtia in Treacher Collins Syndrome Type 4
We describe another patient with TCS4 caused by a recurrentPOLR1B variant, c.3007C#x3e;T; p.Arg1003Cys. Including our patient, all 4 patients with p.(Arg1003Cys) had atresia of the external auditory canal and microtia. All of the reported pathogenic variants inPOLR1B were clustered at only 2 residues. Our patient highlights the genotype-phenotype correlation in TCS4 associated withPOLR1B.Mol Syndromol (Source: Molecular Syndromology)
Source: Molecular Syndromology - March 2, 2021 Category: Molecular Biology Source Type: research

Interstitial Deletion of 2q22.2q22.3 Involving the Entire ZEB2 Gene in a Case of Mowat-Wilson Syndrome
This study emphasizes the significance of CMA in the detection of microdeletions/microduplications and as a screening tool in cases presenting with CHD and extracardiac manifestations. MWS should be suspected in patients presenting with the characteristic facial dysmorphism, developmental delay, seizures, Hirschsprung disease, and congenital heart anomalies, especially those involving the pulmonary arteries or pulmonary valves. It is recommended to include theZEB2 locus in the MLPA microdeletions probes.Mol Syndromol (Source: Molecular Syndromology)
Source: Molecular Syndromology - March 1, 2021 Category: Molecular Biology Source Type: research

Kabuki Syndrome: Identification of Two Novel Variants in KMT2D and KDM6A 
Kabuki syndrome (KS) is a rare genetic disorder characterized by the following 5 crucial symptoms: dysmorphic facial features, growth retardation, skeletal abnormalities, intellectual disability, and dermatoglyphic malformations. Studies show that most of the KS cases are caused by mutations or large deletions in theKMT2D gene, while the other cases show mutations inKDM6A. We studied 2 patients with suspected KS in 2 unrelated families by whole-exome sequencing to identify the possible genetic cause(s) and by Sanger sequencing to validate the identified variants and check the segregation in other members of the families. F...
Source: Molecular Syndromology - February 17, 2021 Category: Molecular Biology Source Type: research

Prevalence and Phenotypic Impact of Robertsonian Translocations
Robertsonian translocations (RTs) result from fusion of 2 acrocentric chromosomes (e.g., 13, 14, 15, 21, 22) and consequential losses of segments of the p arms containing 47S rDNA clusters and transcription factor binding sites. Depending on the position of the breakpoints, the size of these losses vary considerably between types of RTs. The prevalence of RTs in the general population is estimated to be around 1 per 800 individuals, making RTs the most common chromosomal rearrangement in healthy individuals. Based on their prevalence, RTs are classified as “common,” rob(13;14) and rob(14;21), or “rare” (the 8 remai...
Source: Molecular Syndromology - February 17, 2021 Category: Molecular Biology Source Type: research

Identification of Two Novel Frameshift Mutations in Exostosin 1 in Two Families with Multiple Osteochondromas
In this study, we enrolled 2 families with MO. Sanger sequencing revealed 2 novel frameshift mutations – c.1432_1433insCCCCCCT; p.Lys479Profs*44 and c.1431_1431delC; p.S478PfsX10 – in theEXT1 gene detected in 2 families, respectively. Both novel mutations, located in the conserved domain of EXT1 and predicted to be disease causing by informatics programs, were absent in our 200 control cohorts and other public databases. Our study expanded the spectrum ofEXT1 mutations and contributed to genetic diagnosis and counseling of patients with MO.Mol Syndromol (Source: Molecular Syndromology)
Source: Molecular Syndromology - February 16, 2021 Category: Molecular Biology Source Type: research

Two Siblings with Kaufman Oculocerebrofacial Syndrome Resembling Oculoauriculovertebral Spectrum
Kaufman oculocerebrofacial syndrome is a rare autosomal recessive disorder which represents a phenotype mainly involving craniofacial and neurodevelopmental manifestations due toUBE3B gene mutations. The vast majority of the affected individuals exhibit microcephaly, eye abnormalities, and typical facial gestalt including blepharophimosis, ptosis, telecanthus, upslanting palpebral fissures, dysplastic ears, and micrognathia. We encountered 2 siblings in whom severe psychomotor delay, distinctive facial features, hearing loss, and respiratory distress were observed. Some clinical manifestations of the patients, including ep...
Source: Molecular Syndromology - February 5, 2021 Category: Molecular Biology Source Type: research

Camptodactyly-Arthropathy-Coxa Vara-Pericarditis Syndrome Resembling Juvenile Idiopathic Arthritis: A Single-Center Experience from Southern Turkey
Camptodactyly-arthropathy-coxa vara-pericarditis (CACP) syndrome, caused by biallelic pathogenic mutations in thePRG4 gene, is characterized by early-onset camptodactyly, noninflammatory arthropathy, coxa vara deformity, and rarely, pericardial effusion. Herein, we report 3 patients with CACP syndrome from 2 unrelated families. All patients are female, born to consanguineous parents, and had camptodactyly since the first years of their lives. Two patients had a prior diagnosis of juvenile idiopathic arthritis. Hip changes were present in 2 patients, and 2 of 3 patients had undergone surgery for camptodactyly. Routine echoc...
Source: Molecular Syndromology - February 1, 2021 Category: Molecular Biology Source Type: research

Noonan Syndrome with Multiple Lentigines and PTPN11 Mutation: A Case with Intracerebral Hemorrhage
Noonan syndrome with multiple lentigines (NSML), previously known as LEOPARD syndrome, is a rare autosomal dominant disorder with an unknown prevalence. Characteristics of this disease include cutaneous, neurologic, and cardiologic abnormalities. In this case report, we present a 12-year-old girl who was admitted to the emergency department for acute-onset left weakness, unsteady gait, nausea, and vomiting. Her physical exam notably showed left side upper motor neuron signs and dysmetria. CT scan revealed an acute hemorrhage of the right thalamus. Physical exam exhibited several craniofacial dysmorphisms and lentigines. Th...
Source: Molecular Syndromology - January 27, 2021 Category: Molecular Biology Source Type: research

Pharmacological Treatment of Severe Breathing Abnormalities in a Case of HNRNPU Epileptic Encephalopathy
We describe the clinical and genetic features and treatment strategies in a case of EIEE type 54 and severely abnormal breathing pattern. A novel and likely pathogenic c.2277dup, p.(Pro760Serfs*5) variant in the HNRNPU gene was found in a male patient with severe episodes of hyperventilation and apnea, leading to syncope. Combination therapy with acetazolamide, alprazolam and aripiprazole led to significant clinical improvement. Although HNRNPU has not been implicated in breathing control, pathogenic variants in this gene can be associated with the development of abnormal breathing patterns reminiscent of Rett and Pit...
Source: Molecular Syndromology - January 11, 2021 Category: Molecular Biology Source Type: research