First Report of Two Egyptian Patients with Desbuquois Dysplasia due to Homozygous < b > < i > CANT1 < /i > < /b > Mutations
We report on 2unrelated Egyptian patients having the characteristic features of DBQD1 with different expressivity. Patient 1 presented at the age of 45 days with respiratory distress, short limbs, faltering growth, and distinctive facies while patient 2 presented at 5 years of age with short stature and hypospadias. The 2 patients shared radiological features suggestive of DBQD1. Whole-exome sequencing revealed a homozygous frameshift mutation in theCANT1 gene (NM_001159772.1:c.277_278delCT; p.Leu93ValfsTer89) in patient 1 and a homozygous missense mutation (NM_138793.4:c.898C#x3e;T; p.Arg300Cys) in patient 2. Phenotypic v...
Source: Molecular Syndromology - July 22, 2021 Category: Molecular Biology Source Type: research

239-kb Microdeletion Spanning < b > < i > KMT2E < /i > < /b > in a Child with Developmental Delay: Further Delineation of the Phenotype
PathogenicKMT2E variants underly Oapos;Donnell-Luria-Rodan syndrome, a recently described neurodevelopmental disorder characterized by global developmental delay, variable degrees of intellectual disability, and subtle facial dysmorphism. Less common findings include autism, seizures, gastrointestinal (GI) problems, and abnormal head circumference. Occurrence of mostly truncating variants as well as the similar phenotype observed in individuals with deletions spanningKMT2E suggest haploinsufficiency of this gene as a common mechanism for the disorder, while a gain-of-function or dominant-negative effect cannot be ruled out...
Source: Molecular Syndromology - July 22, 2021 Category: Molecular Biology Source Type: research

A Novel Homozygous < b > < i > ALG12 < /i > < /b > Mutation in a Patient with CDG Type Ig: New Report of a Case with a Mild Phenotype
Congenital disorders of glycosylation (CDG) are a group of rare genetic diseases caused by the deficiency of enzymes involved in the biosynthesis or remodeling of the glycan moieties of glycoconjugates. Most of CDG are autosomal recessive; however, few of them show autosomal dominant or X-linked inheritance. ALG12-CDG is an autosomal recessive inherited defect caused by a deficiency in the α-mannosyltransferase, dolichyl-P-mannose: Man7-GlcNAc-2-PP-dolichyl-alpha-6-mannosyltransferase (mannosyltransferase 8), which determines Man7GlcNAc2-PP-dolichol accumulation in tissues including fibroblasts. The clinical features...
Source: Molecular Syndromology - July 20, 2021 Category: Molecular Biology Source Type: research

Partial Trisomy 13q/Monosomy 3p Resulting from a Paternal Reciprocal 3p;13q Translocation in a Boy with Facial Dysmorphism and Hypertrophic Cardiomyopathy
Individuals with 3p deletion show a great clinical variability. Apparently, a 1.5-Mb terminal deletion, including theCRBN andCNTN4 genes, is sufficient to cause this syndrome. Partial trisomy 13q is a rare chromosomal abnormality with a variable phenotypic expression, but in most cases, patients have a phenotype resembling complete trisomy 13. The aim of the present study is to describe a 9-month-old Mexican male patient with 3p deletion/13q duplication and a novel clinical finding. He presented with facial dysmorphism and multiple congenital alterations. Echocardiogram revealed cardiac insufficiency with hypertrophic card...
Source: Molecular Syndromology - July 20, 2021 Category: Molecular Biology Source Type: research

A Mild Phenotype of Mitochondrial DNA Depletion Syndrome Type 13 with a Novel < b > < i > FBXL4 < /i > < /b > Variant
This report shows that patients withFBLX4 gene mutations may present with a milder clinical phenotype than previously reported.Mol Syndromol (Source: Molecular Syndromology)
Source: Molecular Syndromology - July 19, 2021 Category: Molecular Biology Source Type: research

An Apparently Balanced Complex Chromosome Rearrangement Involving Seven Breaks and Four Chromosomes in a Healthy Female and Segregation/Recombination in Her Affected Son
This study aimed to better define the clinical history and prognosis of a patient with this rare category of chromosomal aberration. Our results suggest that the frequency of CCR in the general population may be underestimated; when balanced, they may not have a phenotypic effect. Moreover, they emphasize the need for cytogenetic techniques complementary to chromosomal microarray for proper genetic counseling.Mol Syndromol (Source: Molecular Syndromology)
Source: Molecular Syndromology - July 15, 2021 Category: Molecular Biology Source Type: research

Deletion of 16q22.2q23.3 in a Boy with a Phenotype Reminiscent of Silver-Russell Syndrome
A 15-month-old boy presented with growth and global developmental delay, feeding difficulties, sleep disturbance and several minor anomalies, including a large anterior fontanel, relative macrocephaly, and a triangular face. Clinical suspicion prompted genetic investigations for Silver-Russell syndrome and related disorders. SNP array analysis led to the diagnosis of an approximately 10-Mb large deletion of the long arm in chromosome 16q22.2q23.3. Interstitial deletions of 16q show a wide variability of related features; however, considering the differences in size and location of the deletions in the known patients, the p...
Source: Molecular Syndromology - July 15, 2021 Category: Molecular Biology Source Type: research

Evaluation of Sporadic and Familial Cases with Craniofrontonasal Syndrome: A Wide Clinical Spectrum and Identification of a Novel < b > < i > EFNB1 < /i > < /b > Gene Mutation
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 theEFNB1 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 theEFNB1 gene was performed. A novelEFNB1 gene mutation (c.65delG; p.Cys22SerfsTer24) was detected in a newbo...
Source: Molecular Syndromology - July 12, 2021 Category: Molecular Biology Source Type: research

Publisher's Note
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Source: Molecular Syndromology - June 30, 2021 Category: Molecular Biology Source Type: research

Novel Compound Heterozygous Mutation c.3955_3958dup and c.5825C & #x3e;T in the < b > < i > ATM < /i > < /b > Gene: Clinical Evidence of Ataxia-Telangiectasia and Cancer in a Peruvian Family
Pathogenic and likely pathogenic variants in theATM gene are associated both with Ataxia-telangiectasia disease or ATM syndrome and an increased cancer risk for heterozygous carriers. We identified a novel compound heterozygous mutation c.3955_3958dup (p.Asp1320delinsValTer) and c.5825C#x3e;T (p.Ala1942Val) in theATM gene in a Peruvian patient with progressive ataxia combined with other movement disorders, mild conjunctival telangiectasia and increased alpha-fetoprotein, without history of recurrent infection or immunodeficiency. We also determined the carrier status of the family members, and we were able to detect gastri...
Source: Molecular Syndromology - June 17, 2021 Category: Molecular Biology Source Type: research

Clinical Exome Sequencing Enables Congenital Sialidosis Type II Diagnosis in Two Siblings Presenting with Unreported Clinical Features from a Rare Homozygous Sequence Variant p.(Tyr370Cys) in < b > < i > NEU1 < /i > < /b >
This study allowed us to provide a definitive diagnosis for our patients, increase our understanding of this pathogenic variant, and improve genetic counseling.Mol Syndromol (Source: Molecular Syndromology)
Source: Molecular Syndromology - June 17, 2021 Category: Molecular Biology Source Type: research

Sensenbrenner Syndrome Presenting with Severe Anorexia, Failure to Thrive, Chronic Kidney Disease and Angel-Shaped Middle Phalanges in Two Siblings
Sensenbrenner syndrome is a very rare autosomal recessive disorder caused by variants in genes involved in the functional development of primary cilia. Typical clinical manifestations include craniofacial and skeletal abnormalities, hence the alternative name cranioectodermal dysplasia. Chronic kidney disease due to progressive tubulointerstitial nephritis (nephronophthisis) has been described in these patients. The authors present 2siblings with severe anorexia, failure to thrive, chronic kidney disease, and angel-shaped middle phalanges. Two previously described variants p.(Leu641*) and p.(Asp841Val) were identified in t...
Source: Molecular Syndromology - June 16, 2021 Category: Molecular Biology Source Type: research

New < b > < i > SHH < /i > < /b > and Known < b > < i > SIX3 < /i > < /b > Variants in a Series of Latin American Patients with Holoprosencephaly
Holoprosencephaly (HPE) is the failure of the embryonic forebrain to develop into 2 hemispheres promoting midline cerebral and facial defects. The wide phenotypic variability and causal heterogeneity make genetic counseling difficult. Heterozygous variants with incomplete penetrance and variable expressivity in theSHH,SIX3,ZIC2, andTGIF1 genes explain ∼25% of the known causes of nonchromosomal HPE. We studied these 4 genes and clinically described 27 Latin American families presenting with nonchromosomal HPE. Three newSHH variants and a third knownSIX3 likely pathogenic variant found by Sanger sequencing explained 15% ...
Source: Molecular Syndromology - June 15, 2021 Category: Molecular Biology Source Type: research

A Novel Frameshift Variant of the < b > < i > MITF < /i > < /b > Gene in a Chinese Family with Waardenburg Syndrome Type 2
Waardenburg syndrome (WS) is a rare genetic disorder characterized by varying combinations of sensorineural hearing loss and abnormal pigmentation involving the hair, skin and iris. WS is classified into 4 subtypes (WS1 –WS4) based on additional symptoms. WS2 is characterized by the absence of additional symptoms and is mainly attributed to variants in the microphthalmia-associated transcription factor (MITF) gene. We detected a novel frameshift variant c.1025_1032delGGAACAAG (NM_198159) ofMITF in 5 patients with WS2 from the same Chinese family by using targeted next-generation sequencing and Sanger sequencing. Phen...
Source: Molecular Syndromology - June 14, 2021 Category: Molecular Biology Source Type: research

An 88.8-kb Novel Deletion of 19q13.2 Encompassing the < b > < i > ATP1A3 < /i > < /b > Gene Detected by Array CGH in a Patient with Delayed Psychomotor Development, Generalized Hypotonia and Macrocephaly
We report the case of a male, aged 3 years, presenting with delayed psychomotor development, generalized hypotonia, encephalopathy, delayed myelination in the central nervous system, and poor motor coordination. The array CGH revealed an interstitial deletion of chromosome 19q13.2 with a size of 88.8 kb involving 3 OMIM genes:RABAC1,ARHGEF1, andATP1A3. Heterozygous mutations in theATP1A3 gene are associated with delayed psychomotor development, alternating hemiplegia of childhood type 2 (AHC2), dystonia type 12, and cerebellarataxia-areflexia –pes cavus-optic atrophy-sensorineural hearing loss syndrome, also called C...
Source: Molecular Syndromology - June 10, 2021 Category: Molecular Biology Source Type: research

First Report of a de novo 10q23.31q23.33 Microdeletion: Obesity, Intellectual Disability and Microcephaly
Intellectual disability (ID) is characterized by limited or insufficient development of mental abilities, including intellectual functioning impairments, such as learning and understanding cause-effect relationships. Some cases have ID as the only finding and are called isolated cases. Conversely, cases accompanied by facial dysmorphism, microcephaly, autism spectrum disorder, epilepsy, obesity, and congenital anomalies are called syndromic developmental delay (DD)/ID. Isolated and syndromic DD/ID cases show extreme genetic heterogeneity. Genetic etiology can be detected in approximately 40% of the cases, whereas chromosom...
Source: Molecular Syndromology - June 10, 2021 Category: Molecular Biology Source Type: research

Building the Future Therapies for Down Syndrome: The Third International Conference of the T21 Research Society
Research focused on Down syndrome has increased in the last several years to advance understanding of the consequences of trisomy 21 (T21) on molecular and cellular processes and, ultimately, on individuals with Down syndrome. The Trisomy 21 Research Society (T21RS) is the premier scientific organization for researchers and clinicians studying Down syndrome. The Third International Conference of T21RS, held June 6 –9, 2019, in Barcelona, Spain, brought together 429 scientists, families, and industry representatives to share the latest discoveries on underlying cellular and molecular mechanisms of T21, define cognitiv...
Source: Molecular Syndromology - May 20, 2021 Category: Molecular Biology Source Type: research

Identification of the < b > < i > TTC26 < /i > < /b > Splice Variant in a Novel Complex Ciliopathy Syndrome with Biliary, Renal, Neurological, and Skeletal Manifestations
This report further strengthens the evidence that homozygous variants in theTTC26 gene cause severe ciliopathies with diverse phenotypes. We named this newly characterized condition as BRENS syndrome, which stands for biliary, renal, neurological, and skeletal features.Mol Syndromol (Source: Molecular Syndromology)
Source: Molecular Syndromology - May 11, 2021 Category: Molecular Biology Source Type: research

Goldberg-Shprintzen Syndrome Associated with a Novel Variant in the < b > < i > KIFBP < /i > < /b > Gene
Goldberg-Shprintzen syndrome (GOSHS) is characterized by microcephaly, developmental delay, dysmorphic features, Hirschsprung disease (HSCR), and brain anomalies. The kinesin family binding protein (KIFBP; MIM 60937) gene has been identified as the responsible gene of the syndrome. To date, 16 different biallelicKIFBP mutations have been identified in 34 patients with GOSHS. Even though most of these mutations are nonsense and frameshift, 3 missense mutations have also been described. Here, we report an 18-month-old patient with microcephaly, developmental delay, dysmorphic features and HSCR. Exome analysis was performed t...
Source: Molecular Syndromology - May 7, 2021 Category: Molecular Biology Source Type: research

Deciphering the Pathogenic Nature of Two de novo Sequence Variations in a Patient with Shprintzen-Goldberg Syndrome
We present the unusual molecular findings in a 12-year-old female child with SGS. There was co-occurrence of 2 heterozygous missense variations, c.346G#x3e;A (p.Gly116Arg) and c.687G#x3e;C (p.Lys229Asn), in exon 1 (hotspot) of theSKI gene, which makes this propositus different from all other patients reported in the literature. Both variants were found to be de novo. In silico analysis revealed that both of them are pathogenic, but later on, Gly116Arg was proven to be more pathogenic by various in silico prediction tools. c.687G#x3e;C (p.Lys229Asn) was found as a single report in ExAC in the South Asian population, but c.3...
Source: Molecular Syndromology - May 6, 2021 Category: Molecular Biology Source Type: research

Two Novel Variants and One Previously Reported Variant in the < b > < i > ATP2C1 < /i > < /b > Gene in Chinese Hailey-Hailey Disease Patients
In this study, genomic DNA polymerase chain reaction (PCR) and direct sequencing ofATP2C1 were performed from 3 Chinese pedigrees and 4 sporadic cases of HHD. We detected 3 heterozygous mutations, including 2 novel mutations (c.1673_1674insGTTG and c.2225A#x3e;G) and 1 recurrent nonsense mutation (c.1402C#x3e;T; NM_014382.4). TheATP2C1 gene was also screened in the asymptomatic members of pedigrees. Our results would further expand the mutation spectrum of theATP2C1 gene and be helpful in the genetic counseling of patients with HHD.Mol Syndromol (Source: Molecular Syndromology)
Source: Molecular Syndromology - May 4, 2021 Category: Molecular Biology Source Type: research

Novel Hemizygous Missense Variant of Spermine Synthase ( < b > < i > SMS < /i > < /b > ) Gene Causes Snyder-Robinson Syndrome in a Four-Year-Old Boy
We report a case of SRS with a hemizygous missense variant in theSMS gene,c.334C#x3e;G (p.Pro112Ala), in a 4-year-old boy, who initially developed hypotonia, delayed motor skills, and subsequently epilepsy. This variant inSMS was found to be de novo. To the best of our knowledge, this novelSMS gene variant has never been previously reported in disease-related variation databases, such as ClinVar or HGMD.Mol Syndromol (Source: Molecular Syndromology)
Source: Molecular Syndromology - April 19, 2021 Category: Molecular Biology Source Type: research

Precision Medicine: from Molecular Diagnoses to Treatment Opportunities in Medical Genetics
Mol Syndromol (Source: Molecular Syndromology)
Source: Molecular Syndromology - April 12, 2021 Category: Molecular Biology Source Type: research

Neuroimaging Findings in Patients with < b > < i > EBF3 < /i > < /b > Mutations: Report of Two Cases
We report 2 unrelated cases with novel de novoEBF3 mutations: c.455G#x3e;T (p.Arg152Leu) and c.962dup (p.Tyr321*) to expand the genotype/phenotype correlations of this disorder; clinical, neuropsychological, and MRI studies were used to define the phenotype. IQ was in the normal range and diffusion tensor imaging revealed asymmetric alterations of the longitudinal fasciculus in both cases. Our results demonstrate thatEBF3 mutations can underlie neurodevelopmental disorders without intellectual disability. Long tract abnormalities have not been previously recognized and suggest that they may be an unrecognized and character...
Source: Molecular Syndromology - April 9, 2021 Category: Molecular Biology Source Type: research

Biallelic Mutations in < b > < i > DNAJB11 < /i > < /b > are Associated with Prenatal Polycystic Kidney Disease in a Turkish Family
This study reveals thatDNAJB11 biallelic mutations may cause an antenatal severe form of ARPKD and contributes to understanding theDNAJB11-related ADPKD phenotype. The possibility of ARPKD due to biallelic mutations in ADPKD genes should be considered in genetic counseling.Mol Syndromol (Source: Molecular Syndromology)
Source: Molecular Syndromology - April 1, 2021 Category: Molecular Biology Source Type: research

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 < b > < i > FAM20C < /i > < /b > 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 < b > < i > PNPLA8 < /i > < /b > 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.”...
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 < b > < i > TSC2 < /i > < /b > 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 < b > < i > POLR1B < /i > < /b > , 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 < b > < i > ZEB2 < /i > < /b > 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 < b > < i > KMT2D < /i > < /b > and < b > < i > KDM6A < /i > < /b >
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

Kabuki Syndrome: Identification of Two Novel Variants in < b > < i > KMT2D < /i > < /b > and < b > < i > KDM6A < /i > < /b >
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&rdq...
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 < b > < i > PTPN11 < /i > < /b > 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 < b > < i > HNRNPU < /i > < /b > 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...
Source: Molecular Syndromology - January 11, 2021 Category: Molecular Biology Source Type: research

Contents Vol. 11, 2020
Mol Syndromol 2020;11:I –VI (Source: Molecular Syndromology)
Source: Molecular Syndromology - December 18, 2020 Category: Molecular Biology Source Type: research

The Role of Copy Number Variations and < b > < i > FHIT < /i > < /b > Gene on Phenotypic Characteristics of Cases Diagnosed with Autism Spectrum Disorder
In this study, we aimed to present the clinical characteristics of the cases and parents in more detail, especially in pathogenic CNV cases, which enables us to increase our knowledge on inherited CNVs and genotype-phenotype correlation. We suggest that both genetic and psychiatric evaluation of the parents of the cases is important for better understanding the clinical relevance of the CNV results.Mol Syndromol (Source: Molecular Syndromology)
Source: Molecular Syndromology - December 16, 2020 Category: Molecular Biology Source Type: research

Prenatal Diagnosis of Acromelic Frontonasal Dysostosis
Acromelic frontonasal dysostosis (AFND; MIM #603671) is a rare autosomal dominant genetic disorder caused by a heterozygous mutation in theZSWIM6 (KIAA1577) gene located at chromosome 5q12.1. It is phenotypically characterized by frontonasal malformation with hypertelorism, telecanthus, nasal clefting or bifid nasal tip, wide fontanels and sutures, brachycephaly, and cleft palate. The patients also present with central nervous system malformations such as encephalocele, agenesis of the corpus callosum, or interhemispheric lipoma. Limb malformations can also be found, including preaxial polydactyly of the feet and sometimes...
Source: Molecular Syndromology - December 15, 2020 Category: Molecular Biology Source Type: research

Language Impairment with a Partial Duplication of < b > < i > DOCK8 < /i > < /b >
We report in detail the cognitive and language features of a child with a duplication in the 9p24.3 region, arr[hg19] 9p24.3(266,045 –459,076)×3. The proband exhibits marked expressive and receptive problems, which affect both structural and functional aspects of language. These problems might result from a severe underlying deficit in working memory. Regarding the molecular causes of the observed symptoms, they might result f rom the altered expression of selected genes involved in procedural learning, particularly some of components of the SLIT/ROBO/FOXP2 network, strongly related to the development and evolu...
Source: Molecular Syndromology - December 11, 2020 Category: Molecular Biology Source Type: research

Dystonia and Contractures are Potential Early Signs of < b > < i > CACNA1E < /i > < /b > -Related Epileptic Encephalopathy
In conclusion, the appearance of congenital contractures, areflexia, and movement disorders before the onset of epilepsy may provide key guidance in the diagnosis of epilepticCACNA1E encephalopathy. A genotype-phenotype correlation was found between the presence of movement disorders and severe intellectual disability and the location of the variant in theCACNA1E gene.Mol Syndromol (Source: Molecular Syndromology)
Source: Molecular Syndromology - December 10, 2020 Category: Molecular Biology Source Type: research

Expanding the Phenotype of < b > < i > TUBB2A < /i > < /b > -Related Tubulinopathy: Three Cases of a Novel, Heterozygous < b > < i > TUBB2A < /i > < /b > Pathogenic Variant p.Gly98Arg
We report 3 patients identified by exome and genome sequencing to have a novel, pathogenic, missense variant inTUBB2A (p.Gly98Arg). They presented similarly with intellectual disability, hypotonia, and global developmental delay and varied with respect to the type of cortical brain malformation, seizure history, diagnosis of autism spectrum disorder, and other features. This case series expands the natural history ofTUBB2A-related tubulinopathy while describing the presentation of a novel, pathogenic, missense variant in 3 patients.Mol Syndromol (Source: Molecular Syndromology)
Source: Molecular Syndromology - December 9, 2020 Category: Molecular Biology Source Type: research

Chromothripsis and Duplications as Underappreciated Genomic Gremlins
Mol Syndromol (Source: Molecular Syndromology)
Source: Molecular Syndromology - December 7, 2020 Category: Molecular Biology Source Type: research

A Frameshift Variant in < b > < i > KIAA0825 < /i > < /b > Causes Postaxial Polydactyly
Postaxial polydactyly (PAP) is characterized by counterproductive 5th digit (pinky finger) duplication on hands and/or feet which often leads to functional complications. To date, at least 11 genes involved in causing various types of nonsyndromic polydactylies have been reported. In the present study, a consanguineous family of Sindhi origin with a segregating nonsyndromic form of PAP in an autosomal recessive manner was clinically and genetically evaluated. Genotyping, using polymorphic microsatellite markers, established linkage in the family on chromosome 5q15 harboring theKIAA0825 gene (MIM 617266). Sequence analysis ...
Source: Molecular Syndromology - December 3, 2020 Category: Molecular Biology Source Type: research

Wiedemann-Steiner Syndrome as a Differential Diagnosis of Cornelia de Lange Syndrome Using Targeted Next-Generation Sequencing: A Case Report
Wiedemann-Steiner syndrome (WDSTS) is a rare autosomal dominant disorder with a variable clinical phenotype including synophrys, hypertelorism, thick eyebrows, long eyelashes, wide nasal bridge, long philtrum, hypertrichosis, growth retardation, and intellectual disability. Cornelia de Lange syndrome (CdLS) is a rare disease characterized by synophrys, long eyelashes, limb abnormalities, generalized hirsutism, growth retardation, and intellectual disability. In both WDSTS and CdLS, the malformations are due to transcriptome disturbance caused by defects in the genes encoding the components of chromatin regulation and trans...
Source: Molecular Syndromology - December 1, 2020 Category: Molecular Biology Source Type: research

Novel Findings in Floating-Harbor Syndrome and a Mini-Review of the Literature
Floating-Harbor syndrome (FHS) is a rare autosomal dominant genetic disorder characterized by proportionate short stature with delayed bone maturation, lack of expressive language, and distinctive facial features including a large nose, long eyelashes, deeply set eyes, and triangular face. Mutations in theSRCAP gene cause truncated SNF2-related CREBBP activator protein (SRCAP) and lead to FHS. SRCAP is one of several proteins that act as coactivator for the CREB-binding protein which is associated with Rubinstein-Taybi syndrome (RSTS). This condition likely explains the phenotypic overlap between FHS and RSTS. Herein, we r...
Source: Molecular Syndromology - November 30, 2020 Category: Molecular Biology Source Type: research