scholarly journals Muscle Hemangiomatosis Presenting as a Severe Feature in a Patient with the Pten Mutation: Expanding the Phenotype of Vascular Malformations in Bannayan-Riley-ruvalcaba Syndrome

2012 ◽  
Vol 15 (1) ◽  
pp. 45-50 ◽  
Author(s):  
Y Soysal ◽  
T Acun ◽  
C Lourenço ◽  
W Marques ◽  
M Yakıcıer
Keyword(s):  
Dna Sequencing ◽  
Medical Care ◽  
Clinical Features ◽  
Mutation Analysis ◽  
De Novo ◽  
Vascular Malformations ◽  
Premature Termination Codon ◽  
Vascular Anomalies ◽  
Termination Codon ◽  
Pten Mutation

Muscle Hemangiomatosis Presenting as a Severe Feature in a Patient with the Pten Mutation: Expanding the Phenotype of Vascular Malformations in Bannayan-Riley-ruvalcaba SyndromeBannayan-Riley-Ruvalcaba syndrome (BRRS) is a rare autosomal, dominantly-inherited, hamartoma syndrome with distinct phenotypic features. Mutations in the PTEN gene have been identified in PTEN hamartoma tumor syndromes. Our aim was to determine the correlation of phenotype-genotype relationships in a BRRS case. We have evaluated a PTEN mutation in a patient with vascular anomalies and the phenotypic findings of BRRS. We described an 8-year-old girl with the clinical features of BRRS, specifically with vascular anomalies. The mutation in the PTEN gene was identified by DNA sequencing. In our patient, we defined a de novo nonsense R335X (c.1003 C>T) mutation in exon 8, which results in a premature termination codon. Due to vascular anomalies and hemangioma, the patient's left leg was amputated 1 year after the hemangioma diagnosis. Bannayan - Riley - Ruvalcaba syndrome patients with macrocephaly and vascular anomalies should be considered for PTEN mutation analysis and special medical care.

Vascular anomalies in children

VASA ◽  
2011 ◽  
Vol 40 (6) ◽  
pp. 439-447 ◽  
Author(s):  
Weibel
Keyword(s):  
Early Diagnosis ◽  
Blood Vessels ◽  
Clinical Features ◽  
Vascular Malformations ◽  
Vascular Anomalies ◽  
Multidisciplinary Management ◽  
Benign Neoplasms ◽  
Proliferative Phase ◽  
Spontaneous Involution ◽  
Structural Anomalies

Vascular anomalies are divided in two major categories: tumours (such as infantile hemangiomas) and malformations. Hemangiomas are common benign neoplasms that undergo a proliferative phase followed by stabilization and eventual spontaneous involution, whereas vascular malformations are rare structural anomalies representing morphogenetic errors of developing blood vessels and lymphatics. It is important to properly diagnose vascular anomalies early in childhood because of their distinct differences in morbidity, prognosis and need for a multidisciplinary management. We discuss a number of characteristic clinical features as clues for early diagnosis and identification of associated syndromes.

scholarly journals Identification of Two Independent COL5A1 Variants in Dogs with Ehlers–Danlos Syndrome

Genes ◽  
2019 ◽  
Vol 10 (10) ◽  
pp. 731 ◽  
Author(s):  
Anina Bauer ◽  
John F. Bateman ◽  
Shireen R. Lamandé ◽  
Eric Hanssen ◽  
Shannon G.M. Kirejczyk ◽  
...  
Keyword(s):  
Dna Sequencing ◽  
De Novo ◽  
Clinical Pathology ◽  
Missense Variant ◽  
Premature Termination Codon ◽  
Clinical Analysis ◽  
Joint Hypermobility ◽  
De Novo Mutations ◽  
Ehlers Danlos Syndrome ◽  
Clinical Criteria

The Ehlers–Danlos syndromes (EDS) are a heterogeneous group of heritable disorders affecting connective tissues. The mutations causing the various forms of EDS in humans are well characterized, but the genetic mutations causing EDS-like clinical pathology in dogs are not known, thus hampering accurate clinical diagnosis. Clinical analysis of two independent cases of skin hyperextensibility and fragility, one with pronounced joint hypermobility was suggestive of EDS. Whole-genome sequencing revealed de novo mutations of COL5A1 in both cases, confirming the diagnosis of the classical form of EDS. The heterozygous COL5A1 p.Gly1013ValfsTer260 mutation characterized in case 1 introduced a premature termination codon and would be expected to result in α1(V) mRNA nonsense-mediated mRNA decay and collagen V haploinsufficiency. While mRNA was not available from this dog, ultrastructural analysis of the dermis demonstrated variability in collagen fibril diameter and the presence of collagen aggregates, termed ‘collagen cauliflowers’, consistent with COL5A1 mutations underlying classical EDS. In the second case, DNA sequencing demonstrated a p.Gly1571Arg missense variant in the COL5A1 gene. While samples were not available for further analysis, such a glycine substitution would be expected to destabilize the strict molecular structure of the collagen V triple helix and thus affect protein stability and/or integration of the mutant collagen into the collagen V/collagen I heterotypic dermal fibrils. This is the first report of genetic variants in the COL5A1 gene causing the clinical presentation of EDS in dogs. These data provided further evidence of the important role of collagen V in dermal collagen fibrillogenesis. Importantly, from the clinical perspective, we showed the utility of DNA sequencing, combined with the established clinical criteria, in the accurate diagnosis of EDS in dogs.

scholarly journals Identification of two independent COL5A1 variants in dogs with Ehlers Danlos syndrome

2019 ◽  
Author(s):  
Anina Bauer ◽  
John F. Bateman ◽  
Shireen R. Lamande ◽  
Eric G Hanssen ◽  
Shannon G.M. Kirejczyk ◽  
...  
Keyword(s):  
Dna Sequencing ◽  
De Novo ◽  
Clinical Pathology ◽  
Missense Variant ◽  
Premature Termination Codon ◽  
Clinical Analysis ◽  
Joint Hypermobility ◽  
Ehlers Danlos Syndrome ◽  
Clinical Criteria ◽  
Dermal Collagen

ABSTRACTBACKGROUNDThe Ehlers Danlos syndromes (EDS) are a heterogeneous group of heritable disorders affecting connective tissues. The mutations causing the various forms of EDS in humans are well characterized, but the genetic mutations causing EDS-like clinical pathology in dogs are not known, thus hampering accurate clinical diagnosis.RESULTSClinical analysis of two independent cases of skin hyperextensibility and fragility, one with pronounced joint hypermobility was suggestive of EDS. Whole genome sequencing revealed de novo mutations of COL5A1 in both cases, confirming the diagnosis of the classical form of EDS. The heterozygous COL5A1 p.Gly1013ValfsTer260 mutation characterized in case 1 introduced a premature termination codon and would be expected to result in α1(V) mRNA nonsense-mediated mRNA decay and collagen V haploinsufficiency. While mRNA was not available from this dog, biochemical analysis of the dermis suggested reduced collagen V in the dermis and ultrastructural analysis demonstrated variability in collagen fibril diameter and the presence of collagen aggregates, termed ‘collagen cauliflowers’, consistent with COL5A1 mutations underlying classical EDS. In the second case DNA sequencing demonstrated a p.Gly1571Arg missense variant in the COL5A1 gene. While samples were not available for further analysis, such a glycine substitution would be expected to destabilize the strict molecular structure of the collagen V triple helix and thus affect protein stability and/or integration of the mutant collagen into the collagen V/collagen I heterotypic dermal fibrils.CONCLUSIONSThis is the first report of genetic variants in the COL5A1 gene causing the clinical presentation of EDS in dogs. These data provide further evidence of the important role of collagen V in dermal collagen fibrillogenesis. Importantly from the clinical perspective we show the utility of DNA sequencing, combined with the established clinical criteria, in the accurate diagnosis of EDS in dogs.

CACNA1A Mutation Linking Hemiplegic Migraine and Alternating Hemiplegia of Childhood

Cephalalgia ◽  
2008 ◽  
Vol 28 (8) ◽  
pp. 887-891 ◽  
Author(s):  
B de Vries ◽  
AH Stam ◽  
F Beker ◽  
AMJM van den Maagdenberg ◽  
KRJ Vanmolkot ◽  
...  
Keyword(s):  
Clinical Features ◽  
Molecular Mechanisms ◽  
De Novo ◽  
Monozygotic Twin ◽  
Familial Hemiplegic Migraine ◽  
Hemiplegic Migraine ◽  
Mutation Scanning ◽  
Alternating Hemiplegia Of Childhood ◽  
Neurological Phenotype ◽  
Cacna1a Mutation

Familial hemiplegic migraine (FHM) and alternating hemiplegia of childhood (AHC) are severe neurological disorders that share clinical features. Therefore, FHM genes are candidates for AHC. We performed mutation analysis in the CACNA1A gene in a monozygotic twin pair with clinical features overlapping with both AHC and FHM and identified a novel de novo CACNA1A mutation. We provide the first evidence that a CACNA1A mutation can cause atypical AHC, indicating an overlap of molecular mechanisms causing AHC and FHM. These results also suggest that CACNA1A mutation scanning is indicated in patients with a severe neurological phenotype that includes paroxysmal (alternating) hemiplegia.

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