Interstitial Deletion of 5q22.2q23.1 Including < b > < i > APC < /i > < /b > and < b > < i > TSSK1B < /i > < /b > in a Patient with Adenomatous Polyposis and Asthenoteratozoospermia
Interstitial 5q22 deletions are relatively rare and usually represented by severe clinical features such as developmental delay and growth retardation. Here, we report a 23-year-old male patient, referred to our laboratory for genetic confirmation of possible familial adenomatous polyposis. MLPA and the subsequent array CGH identified an approximately 8-Mb-sized deletion in the 5q22.2q23.1 locus. Further analysis of the deleted region and the genes within suggested a possible role for theTSSK1B (testis-specific serine/threonine kinase 1) gene in the patient's reproductive capacity. Semen analysis confirmed that the patient...
Source: Molecular Syndromology - August 21, 2018 Category: Molecular Biology Source Type: research
A Novel GDF6 Mutation in a Family with Multiple Synostoses Syndrome without Hearing Loss
A 4-generation family with multiple synostoses syndrome type 4 (SYNS4) is reported, the third family identified so far. The phenotype segregated with a previously undescribed Asn399Lys (c.1197C>A) substitution inGDF6. N399 is part of a hydrophobic pocket critical for binding the BMP/GDF antagonist noggin. The N399K substitution renders GDF6 more similar to noggin-resistant members of the BMP family, namely GDF2 and BMP10, both of which contain lysine in the corresponding position. To further define the SYNS4 phenotype, we examined 6 of 9 affected family members. The phenotype was carpal and tarsal synostoses with painful f...
Source: Molecular Syndromology - August 15, 2018 Category: Molecular Biology Source Type: research
A Novel < b > < i > GDF6 < /i > < /b > Mutation in a Family with Multiple Synostoses Syndrome without Hearing Loss
A 4-generation family with multiple synostoses syndrome type 4 (SYNS4) is reported, the third family identified so far. The phenotype segregated with a previously undescribed Asn399Lys (c.1197C>A) substitution inGDF6. N399 is part of a hydrophobic pocket critical for binding the BMP/GDF antagonist noggin. The N399K substitution renders GDF6 more similar to noggin-resistant members of the BMP family, namely GDF2 and BMP10, both of which contain lysine in the corresponding position. To further define the SYNS4 phenotype, we examined 6 of 9 affected family members. The phenotype was carpal and tarsal synostoses with painful f...
Source: Molecular Syndromology - August 14, 2018 Category: Molecular Biology Source Type: research
Genetic Causes of Craniosynostosis: An Update
In 1993, Jabs et al. were the first to describe a genetic origin of craniosynostosis. Since this discovery, the genetic causes of the most common syndromes have been described. In 2015, a total of 57 human genes were reported for which there had been evidence that mutations were causally related to craniosynostosis. Facilitated by rapid technological developments, many others have been identified since then. Reviewing the literature, we characterize the most common craniosynostosis syndromes followed by a description of the novel causes that were identified between January 2015 and December 2017.Mol Syndromol (Source: Molecular Syndromology)
Source: Molecular Syndromology - August 14, 2018 Category: Molecular Biology Source Type: research
Could Dissimilar Phenotypic Effects of ACTB Missense Mutations Reflect the Actin Conformational Change Two Novel Mutations and Literature Review
We describe 2 different novel de novo missenseACTBmutations, c.208C>G (p.Pro70Ala) and c.511C>T (p.Leu171Phe), found by trio exome sequencing analysis of 2 unrelated patients: an 8-year-old boy with a suspected BRWS and a 4-year-old girl with unclear developmental disorder. The mutated residue in the first case is situated in the actin H-loop, which is involved in actin polymerization. The mutated residue in the second case (p.Leu171Phe) is found at the actin barbed end in the W-loop, important for binding to profilin and other actin-binding molecules. While the boy presented with a typical BRWS facial appearance, the girl...
Source: Molecular Syndromology - August 9, 2018 Category: Molecular Biology Source Type: research
Could Dissimilar Phenotypic Effects of < b > < i > ACTB < /i > < /b > Missense Mutations Reflect the Actin Conformational Change? Two Novel Mutations and Literature Review
We describe 2 different novel de novo missenseACTBmutations, c.208C>G (p.Pro70Ala) and c.511C>T (p.Leu171Phe), found by trio exome sequencing analysis of 2 unrelated patients: an 8-year-old boy with a suspected BRWS and a 4-year-old girl with unclear developmental disorder. The mutated residue in the first case is situated in the actin H-loop, which is involved in actin polymerization. The mutated residue in the second case (p.Leu171Phe) is found at the actin barbed end in the W-loop, important for binding to profilin and other actin-binding molecules. While the boy presented with a typical BRWS facial appearance, the girl...
Source: Molecular Syndromology - August 8, 2018 Category: Molecular Biology Source Type: research
An Interstitial 17q11.2 de novo Deletion Involving the CDK5R1 Gene in a High-Functioning Autistic Patient
We describe a 32-year-old male patient diagnosed with high-functioning autism spectrum disorder carrying a de novo 196-kb interstitial deletion at chromosome 17q11.2. The deletion was detected by array CGH (180K Agilent) and confirmed by quantitative PCR on genomic DNA. The deleted region spans the entirePSMD11 andCDK5R1 genes and partially theMYO1D gene. TheCDK5R1 gene encodes for a regulatory subunit of the cyclin-dependent kinase 5 responsible for its brain-specific activation. This gene has been previously associated with intellectual disability in humans. A reduction inCDK5R1 transcript was detected, consistent with t...
Source: Molecular Syndromology - August 2, 2018 Category: Molecular Biology Source Type: research
An Interstitial 17q11.2 de novo Deletion Involving the < b > < i > CDK5R1 < /i > < /b > Gene in a High-Functioning Autistic Patient
We describe a 32-year-old male patient diagnosed with high-functioning autism spectrum disorder carrying a de novo 196-kb interstitial deletion at chromosome 17q11.2. The deletion was detected by array CGH (180K Agilent) and confirmed by quantitative PCR on genomic DNA. The deleted region spans the entirePSMD11 andCDK5R1 genes and partially theMYO1D gene. TheCDK5R1 gene encodes for a regulatory subunit of the cyclin-dependent kinase 5 responsible for its brain-specific activation. This gene has been previously associated with intellectual disability in humans. A reduction inCDK5R1 transcript was detected, consistent with t...
Source: Molecular Syndromology - July 31, 2018 Category: Molecular Biology Source Type: research
An FDA-Approved Drug Screen for Compounds Influencing Craniofacial Skeletal Development and Craniosynostosis
Neural crest stem/progenitor cells (NCSCs) populate a variety of tissues, and their dysregulation is implicated in several human diseases including craniosynostosis and neuroblastoma. We hypothesised that small molecules that inhibit NCSC induction or differentiation may represent potential therapeutically relevant drugs in these disorders. We screened 640 FDA-approved compounds currently in clinical use for other conditions to identify those which disrupt development of NCSC-derived skeletal elements that form the zebrafish jaw. In the primary screen, we used heterozygous transgenicsox10:gfpzebrafish to directly visualise...
Source: Molecular Syndromology - July 20, 2018 Category: Molecular Biology Source Type: research
A Novel Mutation of KIF11 in a Child with 22q11.2 Deletion Syndrome Associated with MCLMR
In this study, for the first time, we describe the co-occurrence of aKIF11 mutation and 22q11.2 deletion syndrome in a patient with MCLMR.Mol Syndromol (Source: Molecular Syndromology)
Source: Molecular Syndromology - July 19, 2018 Category: Molecular Biology Source Type: research
Craniofrontonasal Syndrome Caused by Introduction of a Novel uATG in the 5 ′UTR of EFNB1
Craniofrontonasal syndrome (CFNS) is an X-linked disorder caused byEFNB1 mutations in which females are more severely affected than males. Severe male phenotypes are associated with mosaicism, supporting cellular interference for sex bias in this disease. Although many variants have been found in the coding region ofEFNB1, only 2 pathogenic variants have been identified in the same nucleotide in 5 ′UTR, disrupting the stop codon of an upstream open reading frame (uORF). uORFs are known to be part of a wide range of post-transcriptional regulation processes, and just recently, their association with human diseases has com...
Source: Molecular Syndromology - July 12, 2018 Category: Molecular Biology Source Type: research
Mouse Models of Syndromic Craniosynostosis
Craniosynostosis is a common craniofacial birth defect. This review focusses on the advances that have been achieved through studying the pathogenesis of craniosynostosis using mouse models. Classic methods of gene targeting which generate individual gene knockout models have successfully identified numerous genes required for normal development of the skull bones and sutures. However, the study of syndromic craniosynostosis has largely benefited from the production of knockin models that precisely mimic human mutations. These have allowed the detailed investigation of downstream events at the cellular and molecular level ...
Source: Molecular Syndromology - July 12, 2018 Category: Molecular Biology Source Type: research
Syndromes Hidden within the 16p11.2 Deletion Region
Mol Syndromol 2018;9:171-174 (Source: Molecular Syndromology)
Source: Molecular Syndromology - July 12, 2018 Category: Molecular Biology Source Type: research
An Overview of Modelling Craniosynostosis Using the Finite Element Method
Craniosynostosis is a medical condition caused by the early fusion of the cranial joint. The finite element method (FEM) is a computational technique that can answer a variety of “what if” questions in relation to the biomechanics of this condition. The aim of this study was to review the current literature that has used FEM to investigate the biomechanics of any aspect of craniosynostosis, being its development or its reconstruction. This review highlights that a relati vely small number of studies (n = 10) has used FEM to investigate the biomechanics of craniosynostosis. Current studies set a good foundation for the ...
Source: Molecular Syndromology - July 10, 2018 Category: Molecular Biology Source Type: research
Structural Genome Variations Related to Craniosynostosis
Craniosynostosis refers to a condition during early development in which one or more of the fibrous sutures of the skull prematurely fuse by turning into bone, which produces recognizable patterns of cranial shape malformations depending on which suture(s) are affected. In addition to cases with isolated cranial dysmorphologies, craniosynostosis appears in syndromes that include skeletal features of the eyes, nose, palate, hands, and feet as well as impairment of vision, hearing, and intellectual development. Approximately 85% of the cases are nonsyndromic sporadic and emerge after de novo structural genome rearrangements ...
Source: Molecular Syndromology - July 6, 2018 Category: Molecular Biology Source Type: research
