A phenotype intermediate between Desbuquois dysplasia and diastrophic dysplasia secondary to mutations in <i>DTDST</i>

Panzer, Karin; Lachman, Ralph S.; Modaff, Peggy; Pauli, Richard M.

doi:10.1002/ajmg.a.32543

Cited by 11 publications

(18 citation statements)

References 18 publications

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“…This is shown here between DTD and rMED (Fig. 3), but it is also true for the other SLC26A6 ‐related dysplasias (between ACG1B and AO2 and between AO2 and DTD) (22–26). The spectrum of SLC26A2 ‐related dysplasias can hence be described as a continuum, while also continuously expanding (27).…”

Section: Discussionsupporting

confidence: 71%

Clinical and molecular characterization of Diastrophic Dysplasia in the Portuguese population

et al. 2010

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Barbosa M, Sousa AB, Medeira A, Lourenço T, Saraiva J, Pinto‐Basto J, Soares G, Fortuna AM, Superti‐Furga A, Mittaz L, Reis‐Lima M, Bonafé L. Clinical and molecular characterization of Diastrophic Dysplasia in the Portuguese population. SLC26A2‐related dysplasias encompass a spectrum of diseases: from lethal achondrogenesis type 1B (ACG1B; MIM #600972) and atelosteogenesis type 2 (AO2; MIM #256050) to classical diastrophic dysplasia (cDTD; MIM #222600) and recessive multiple epiphyseal dysplasia (rMED; MIM #226900). This study aimed at characterizing clinically, radiologically and molecularly 14 patients affected by non‐lethal SLC26A2‐related dysplasias and at evaluating genotype–phenotype correlation. Phenotypically, eight patients were classified as cDTD, four patients as rMED and two patients had an intermediate phenotype (mild DTD – mDTD, previously ‘DTD variant'). The Arg279Trp mutation was present in all patients, either in homozygosity (resulting in rMED) or in compound heterozygosity with the known severe alleles Arg178Ter or Asn425Asp (resulting in DTD) or with the mutation c.727‐1G>C (causing mDTD). The ‘Finnish mutation’, c.‐26+2T>C, and the p.Cys653Ser, both frequent mutations in non‐Portuguese populations, were not identified in any of the patients of our cohort and are probably very rare in the Portuguese population. A targeted mutation analysis for p.Arg279Trp and p.Arg178Ter in the Portuguese population allows the identification of approximately 90% of the pathogenic alleles.

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Section: Discussionsupporting

confidence: 71%

Clinical and molecular characterization of Diastrophic Dysplasia in the Portuguese population

et al. 2010

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“…An intermediate phenotype of DBQD, diastrophic dysplasia, and recessive multiple epiphyseal dysplasia, including the monkey wrench appearance of the proximal femora, have been identified with compound heterozygote DTDST gene mutations. 16,17 We identified three novel CANT1 gene mutations in our patients, all located within exon 2 of the gene. Two were frameshift mutations with predicted stop codons after 89 and 13 missense amino acid residues, respectively, and were expected to cause complete loss of protein function, probably through nonsense-mediated RNA decay as disease-causing mechanism.…”

Section: Discussionmentioning

confidence: 85%

Desbuquois dysplasia type I and fetal hydrops due to novel mutations in the CANT1 gene

et al. 2011

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We report on three hydropic fetuses of 17, 22 and 25 gestational weeks from three distinct families presenting with Desbuquois dysplasia type 1. All fetuses showed brachymelia and characteristic dysmorphic features. X-ray studies revealed d-shaped extraphalangeal bones and disease-specific prominence of the lesser trochanter, varying in severity with fetal age. Early lethal manifestation of the disorder was reflected in lung hypoplasia and in early death of similarly affected siblings in cases 1 and 2. All families were German Caucasians by descent. Sequence analysis of the CANT1 gene revealed two frameshift mutations, c.228_229insC and c.277_278delCT, in homozygous and compound heterozygous configuration, respectively, and a homozygously novel missense mutation, c.336C4A (p.D112E), located within a highly conserved region of exon 2. Haplotype analyses by high-resolution single-nucleotide polymorphism array showed that the haplotype associated with c.228_229insC may be traced to a single founder in the German population.

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“…We analyzed recent publications on the intermediate DTDST forms between Desbuquois dysplasia, diastrophic dysplasia and MED [Bieganski et al, 2000; Miyake et al, 2008; Panzer et al, 2008; Al Kaissi et al, 2009]. According to the DTDST severity continuum proposed by Panzer et al 2008, the phenotype of our patients is in the middle between “diastrophic dysplasia variant” and MED.…”

Section: Discussionmentioning

confidence: 98%

New intermediate phenotype between MED and DD caused by compound heterozygous mutations in the DTDST gene

Czarny-Ratajczak

Biegański

Rogala

et al. 2010

American J of Med Genetics Pt A

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DTDST mutations cause a spectrum of diastrophic dysplasia disorders characterized by defects of proteoglycans sulfation. Reduction of sulfate/chloride antiporter activity is manifested by lower sulfate uptake and depends on a combination of mutations in DTDST. We analyzed a family with an autosomal recessive form of bone dysplasia. Three affected brothers from this family are compound heterozygotes for C653S/A715V mutations. We classified their phenotype as a new intermediate form between diastrophic dysplasia and multiple epiphyseal dysplasia, manifested by shortening of stature, metatarsus adductus/club foot, mild brachydactyly, proximally placed thumbs and clinodactyly of the fifth fingers. Radiographs document platyspondyly most marked in the lower thoracic and upper lumbar spine, epiphyseal dysplasia affecting predominantly the femoral heads, widening of the metaphyses, narrow growth cartilage and multilayered patellae. Exaggerated lesser trochanters of femur, that is, "monkey wrench" sign, elevated greater trochanters, thin upper pubic rami, grossly normal carpal/tarsal bones and severe, early onset osteoarthritis were other notable features.

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A phenotype intermediate between Desbuquois dysplasia and diastrophic dysplasia secondary to mutations in DTDST

Cited by 11 publications

References 18 publications

Clinical and molecular characterization of Diastrophic Dysplasia in the Portuguese population

Clinical and molecular characterization of Diastrophic Dysplasia in the Portuguese population

Desbuquois dysplasia type I and fetal hydrops due to novel mutations in the CANT1 gene

New intermediate phenotype between MED and DD caused by compound heterozygous mutations in the DTDST gene

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