Keutel syndrome: Report of two novel MGP mutations and discussion of clinical overlap with arylsulfatase E deficiency and relapsing polychondritis

K. Nicole Weaver, Moussa El Hallek, Robert J. Hopkin, Kristen L. Sund, Michael Henrickson, Daniela del Gaudio, Adnan Yuksel, Gül Ozbilen Acar, Michael B. Bober, Jinoh Kim, Simeon Boyd

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Keutel syndrome is a rare, autosomal recessive disorder characterized by diffuse cartilage calcification, peripheral pulmonary artery stenosis, midface retrusion, and short distal phalanges. To date, 28 patients from 18 families have been reported, and five mutations in the matrix Gla protein gene (MGP) have been identified. The matrix Gla protein (MGP) is a vitamin K-dependent extracellular protein that functions as a calcification inhibitor through incompletely understood mechanisms. We present the clinical manifestations of three affected siblings from a consanguineous Turkish family, in whom we detected the sixth MGP mutation (c.79G>T, which predicts p.E27X) and a fourth unrelated patient in whom we detected the seventh MGP mutation, a partial deletion of exon 4. Both mutations predict complete loss of MGP function. One of the patients presented initially with a working diagnosis of relapsing polychondritis. Clinical features suggestive of Keutel syndrome were also observed in one additional unrelated patient who was later found to have a deletion of arylsulfatase E, consistent with a diagnosis of X-linked recessive chondrodysplasia punctata. Through a discussion of these cases, we highlight the clinical overlap of Keutel syndrome, X-linked chondrodysplasia punctata, and the inflammatory disease relapsing polychondritis.

Original languageEnglish (US)
Pages (from-to)1062-1068
Number of pages7
JournalAmerican Journal of Medical Genetics, Part A
Volume164
Issue number4
DOIs
StatePublished - 2014

Fingerprint

Relapsing Polychondritis
Chondrodysplasia Punctata
Mutation
Genes
Vitamin K
Cartilage
Siblings
Exons
X-Linked Chondrodysplasia Punctata 1
matrix Gla protein
Keutel syndrome
Proteins

Keywords

  • ARSE
  • Chondrodysplasia punctata
  • Keutel
  • MGP
  • Relapsing polychondritis

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics
  • Medicine(all)

Cite this

Keutel syndrome : Report of two novel MGP mutations and discussion of clinical overlap with arylsulfatase E deficiency and relapsing polychondritis. / Weaver, K. Nicole; El Hallek, Moussa; Hopkin, Robert J.; Sund, Kristen L.; Henrickson, Michael; del Gaudio, Daniela; Yuksel, Adnan; Acar, Gül Ozbilen; Bober, Michael B.; Kim, Jinoh; Boyd, Simeon.

In: American Journal of Medical Genetics, Part A, Vol. 164, No. 4, 2014, p. 1062-1068.

Research output: Contribution to journalArticle

Weaver, KN, El Hallek, M, Hopkin, RJ, Sund, KL, Henrickson, M, del Gaudio, D, Yuksel, A, Acar, GO, Bober, MB, Kim, J & Boyd, S 2014, 'Keutel syndrome: Report of two novel MGP mutations and discussion of clinical overlap with arylsulfatase E deficiency and relapsing polychondritis', American Journal of Medical Genetics, Part A, vol. 164, no. 4, pp. 1062-1068. https://doi.org/10.1002/ajmg.a.36390
Weaver, K. Nicole ; El Hallek, Moussa ; Hopkin, Robert J. ; Sund, Kristen L. ; Henrickson, Michael ; del Gaudio, Daniela ; Yuksel, Adnan ; Acar, Gül Ozbilen ; Bober, Michael B. ; Kim, Jinoh ; Boyd, Simeon. / Keutel syndrome : Report of two novel MGP mutations and discussion of clinical overlap with arylsulfatase E deficiency and relapsing polychondritis. In: American Journal of Medical Genetics, Part A. 2014 ; Vol. 164, No. 4. pp. 1062-1068.
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