TY - JOUR
T1 - Keutel syndrome
T2 - Report of two novel MGP mutations and discussion of clinical overlap with arylsulfatase E deficiency and relapsing polychondritis
AU - Weaver, K. Nicole
AU - El Hallek, Moussa
AU - Hopkin, Robert J.
AU - Sund, Kristen L.
AU - Henrickson, Michael
AU - del Gaudio, Daniela
AU - Yuksel, Adnan
AU - Acar, Gül Ozbilen
AU - Bober, Michael B.
AU - Kim, Jinoh
AU - Boyadjiev, Simeon A.
PY - 2014
Y1 - 2014
N2 - 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.
AB - 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.
KW - ARSE
KW - Chondrodysplasia punctata
KW - Keutel
KW - MGP
KW - Relapsing polychondritis
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U2 - 10.1002/ajmg.a.36390
DO - 10.1002/ajmg.a.36390
M3 - Article
C2 - 24458983
AN - SCOPUS:84896313502
SN - 1552-4825
VL - 164
SP - 1062
EP - 1068
JO - American Journal of Medical Genetics, Part A
JF - American Journal of Medical Genetics, Part A
IS - 4
ER -