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.

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 NEU1 
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 SHH and Known SIX3 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% of...
Source: Molecular Syndromology - June 15, 2021 Category: Molecular Biology Source Type: research

A Novel Frameshift Variant of the MITF 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. Phenotyp...
Source: Molecular Syndromology - June 14, 2021 Category: Molecular Biology Source Type: research

An 88.8-kb Novel Deletion of 19q13.2 Encompassing the ATP1A3 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 CAPOS...
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 cognitive an...
Source: Molecular Syndromology - May 20, 2021 Category: Molecular Biology Source Type: research

Identification of the TTC26 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 KIFBP 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 ATP2C1 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 ( SMS ) 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 EBF3 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 DNAJB11 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