(1/10) Zinc metalloproteinase, ZMPSTE24, is mutated in mandibuloacral dysplasia.

Mandibuloacral dysplasia (MAD; OMIM 248370) is a rare, genetically and phenotypically heterogeneous, autosomal recessive disorder characterized by skeletal abnormalities including hypoplasia of the mandible and clavicles, acro-osteolysis, cutaneous atrophy and lipodystrophy. A homozygous missense mutation, Arg527His, in the LMNA gene which encodes nuclear lamina proteins lamins A and C has been reported in patients with MAD and partial lipodystrophy. We studied four patients with MAD who had no mutations in the LMNA gene. We now show compound heterozygous mutations, Phe361fsX379 and Trp340Arg, in the zinc metalloproteinase (ZMPSTE24) gene in one of the four patients who had severe MAD associated with progeroid appearance and generalized lipodystrophy. ZMPSTE24 is involved in post-translational proteolytic cleavage of carboxy terminal residues of farnesylated prelamin A in two steps to form mature lamin A. Deficiency of Zmpste24 in mice causes accumulation of prelamin A and phenotypic features similar to MAD. The yeast homolog, Ste24, has a parallel role in processing of prenylated mating pheromone a-factor. Since human ZMPSTE24 can also process a-factor when expressed in yeast, we assessed the functional significance of the two ZMPSTE24 mutations in the yeast to complement the mating defect of the haploid MATa yeast lacking STE24 and Ras-converting enzyme 1 (RCE1; another prenylprotein-specific endoprotease) genes. The ZMPSTE24 mutant construct, Phe361fsX379, was inactive in complementing the yeast a-factor but the mutant, Trp340Arg, was partially active compared to the wild type ZMPSTE24 construct. We conclude that mutations in ZMPSTE24 may cause MAD by affecting prelamin A processing.  (+info)

(2/10) Faun tail naevus: a cutaneous marker of spinal dysraphism.

We describe three cases (one male and two females) of faun tail nevi, which is one of the most important cutaneous marker of spinal dysraphism. One of the patients presented with acro-osteolysis leading to auto amputation of the toes of the left foot, which required operative intervention. This lays stress on the early recognition of lumbar paraspinal skin lesions and early treatment to avoid irreversible sequelae.  (+info)

(3/10) Radiological bone lesions in fibroblastic rheumatism; case report.

INTRODUCTION: Fibroblastic rheumatism (FR) is a rare disease characterized by polyarthralgia associated with painless subcutaneous nodules, sclerodactyly and finger contractures. CASE REPORT: A 45-year-old man presented with peripheral vascular disease, polyarthralgia and subcutaneous nodules. The diagnosis of FR was confirmed by histological examination of a biopsy sample of a nodule, which showed myofibroblast proliferation. Radiographs of both hands showed bilateral erosion of the distal and proximal interphalangeal joints, of the right trapezium bone and acro-osteolysis of the third phalanx of the right-hand second finger. COMMENTS: Although the clinical features of FR have now been well described, the literature includes few radiological descriptions. In most reported cases, radiographs are normal at disease onset. Joint radiographs performed later usually show bone destruction of the hands and feet.  (+info)

(4/10) Acro-osteolysis and mononeuritis multiplex as a presenting symptom of systemic angiitis of Wegener's type.

Wegener's granulomatosis is a multisystem disorder involving small- and medium-sized vessels, leading to granuloma formation and involvement of upper and lower respiratory tract with or without glomerulonephritis. However, limited forms of angiitis and granulomatosis of the Wegener's type with oligosymptomatic and atypical site involvement are known to occur. We present here a rare case of limited form of angiitis and granulomatosis of Wegener's type who presented sequentially with spontaneous resorption of digits with acro-osteolysis and mononeuritis multiplex over a period of 10 months. His vasculitic workup revealed high proteinase 3 antibodies (c-ANCA) titers and an almost asymptomatic lung involvement, detected on high-resolution computed tomography of chest. The patient was aggressively treated with immunosuppressive therapy, following which he showed good improvement.  (+info)

(5/10) Type B mandibuloacral dysplasia with congenital myopathy due to homozygous ZMPSTE24 missense mutation.

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(6/10) Osteoblasts from a mandibuloacral dysplasia patient induce human blood precursors to differentiate into active osteoclasts.

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(7/10) Effect of zoledronic acid on acro-osteolysis and osteoporosis in a patient with Hajdu-Cheney syndrome.

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(8/10) Salim Haim and the syndrome that bears his name.

Professor Salim Haim (1919-1983) was a well-known dermatologist. In 1965, Dr. Haim and Dr. Munk, a radiologist, reported a rare congenital type of genodermatosis, later known as Haim-Munk syndrome. This syndrome is characterized by palmoplantar keratosis, pes planus, onychogryphosis, periodontitis, arachnodactyly, and acroosteolysis. This report discusses Haim and Haim-Munk syndrome.  (+info)

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