Congenital contractural arachnodactyly with neurogenic muscular atrophy: case report

Scola, Rosana Hermínia; Werneck, Lineü Cesar; Iwamoto, Fábio M.; Ribas, Letícia Cristine; Raskin, Salmo; Neto, Ylmar Correa

doi:10.1590/s0004-282x2001000200022

Cited by 6 publications

(5 citation statements)

References 13 publications

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“…Muscular abnormalities have been reported in CCA patients. Muscle hypoplasia, particularly of the calf muscles, is a clinical feature of CCA [5] while atrophy has been reported in CCA [20], or syndromes with some features of CCA [21].…”

Section: Discussionmentioning

confidence: 99%

ENU Mutagenesis Reveals a Novel Phenotype of Reduced Limb Strength in Mice Lacking Fibrillin 2

Miller

Neilan

Chia³

et al. 2010

PLoS ONE

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BackgroundFibrillins 1 (FBN1) and 2 (FBN2) are components of microfibrils, microfilaments that are present in many connective tissues, either alone or in association with elastin. Marfan's syndrome and congenital contractural arachnodactyly (CCA) result from dominant mutations in the genes FBN1 and FBN2 respectively. Patients with both conditions often present with specific muscle atrophy or weakness, yet this has not been reported in the mouse models. In the case of Fbn1, this is due to perinatal lethality of the homozygous null mice making measurements of strength difficult. In the case of Fbn2, four different mutant alleles have been described in the mouse and in all cases syndactyly was reported as the defining phenotypic feature of homozygotes.Methodology/Principal FindingsAs part of a large-scale N-ethyl-N-nitrosourea (ENU) mutagenesis screen, we identified a mouse mutant, Mariusz, which exhibited muscle weakness along with hindlimb syndactyly. We identified an amber nonsense mutation in Fbn2 in this mouse mutant. Examination of a previously characterised Fbn2-null mutant, Fbn2fp, identified a similar muscle weakness phenotype. The two Fbn2 mutant alleles complement each other confirming that the weakness is the result of a lack of Fbn2 activity. Skeletal muscle from mutants proved to be abnormal with higher than average numbers of fibres with centrally placed nuclei, an indicator that there are some regenerating muscle fibres. Physiological tests indicated that the mutant muscle produces significantly less maximal force, possibly as a result of the muscles being relatively smaller in Mariusz mice.ConclusionsThese findings indicate that Fbn2 is involved in integrity of structures required for strength in limb movement. As human patients with mutations in the fibrillin genes FBN1 and FBN2 often present with muscle weakness and atrophy as a symptom, Fbn2-null mice will be a useful model for examining this aspect of the disease process further.

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Section: Discussionmentioning

confidence: 99%

ENU Mutagenesis Reveals a Novel Phenotype of Reduced Limb Strength in Mice Lacking Fibrillin 2

Miller

Neilan

Chia³

et al. 2010

PLoS ONE

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“…CCA is a well-characterized autosomal dominant disorder with variability in the clinical expression and intragenic heterogeneity [ 21 ]. CCA is phenotypically related to MFS, including tall stature, marfanoid habitus, arachnodactyly, camptodactyly, kyphoscoliosis and pectus excavatum [ 22 ].…”

Section: Discussionmentioning

confidence: 99%

Identification of a Novel Missense FBN2 Mutation in a Chinese Family with Congenital Contractural Arachnodactyly Using Exome Sequencing

Deng

Lü

et al. 2016

PLoS ONE

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Congenital contractural arachnodactyly (CCA, OMIM 121050), also known as Beals-Hecht syndrome, is an autosomal dominant disorder of connective tissue. CCA is characterized by arachnodactyly, dolichostenomelia, pectus deformities, kyphoscoliosis, congenital contractures and a crumpled appearance of the helix of the ear. The aim of this study is to identify the genetic cause of a 4-generation Chinese family of Tujia ethnicity with congenital contractural arachnodactyly by exome sequencing. The clinical features of patients in this family are consistent with CCA. A novel missense mutation, c.3769T>C (p.C1257R), in the fibrillin 2 gene (FBN2) was identified responsible for the genetic cause of our family with CCA. The p.C1257R mutation occurs in the 19th calcium-binding epidermal growth factor-like (cbEGF) domain. The amino acid residue cysteine in this domain is conserved among different species. Our findings suggest that exome sequencing is a powerful tool to discover mutation(s) in CCA. Our results may also provide new insights into the cause and diagnosis of CCA, and may have implications for genetic counseling and clinical management.

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“…CCA is an established autosomal dominant genetic disease [9] characterized by contractures, arachnodactyly, dolichostenomelia, scoliosis, crumpled ears and pectus deformities [10]. The clinical symptoms are similar, but genetically distinct, to MFS.…”

Section: Discussionmentioning

confidence: 99%

Whole exome sequencing identifies a novel missense FBN2 mutation co-segregating in a four-generation Chinese family with congenital contractural arachnodactyly

et al. 2016

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BackgroundCongenital contractural arachnodactyly (CCA) is an autosomal dominant rare genetic disease, estimated to be less than 1 in 10,000 worldwide. People with this condition often have permanently bent joints (contractures), like bent fingers and toes (camptodactyly).Case presentationIn this study, we investigated the genetic aetiology of CCA in a four-generation Chinese family. The blood samples were collected from 22 living members of the family in the Yangquan County, Shanxi Province, China. Of those, eight individuals across 3 generations have CCA. Whole exome sequencing (WES) identified a missense mutation involving a T-to-G transition at position 3229 (c.3229 T > G) in exon 25 of the FBN2 gene, resulting in a Cys 1077 to Gly change (p.C1077G). This previously unreported mutation was found in all 8 affected individuals, but absent in 14 unaffected family members. SIFT/PolyPhen prediction and protein conservation analysis suggest that this novel mutation is pathogenic. Our study extended causative mutation spectrum of FBN2 gene in CCA patients.ConclusionsThis study has identified a novel missense mutation in FBN2 gene (p.C1077G) resulting in CCA in a family of China.

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Congenital contractural arachnodactyly with neurogenic muscular atrophy: case report

Cited by 6 publications

References 13 publications

ENU Mutagenesis Reveals a Novel Phenotype of Reduced Limb Strength in Mice Lacking Fibrillin 2

ENU Mutagenesis Reveals a Novel Phenotype of Reduced Limb Strength in Mice Lacking Fibrillin 2

Identification of a Novel Missense FBN2 Mutation in a Chinese Family with Congenital Contractural Arachnodactyly Using Exome Sequencing

Whole exome sequencing identifies a novel missense FBN2 mutation co-segregating in a four-generation Chinese family with congenital contractural arachnodactyly

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