Increased release and activity of matrix metalloproteinase‐9 in patients with mandibuloacral dysplasia type A, a rare premature ageing syndrome

Lombardi, Francesca; Fasciglione, Giovanni Francesco; D’Apice, Maria Rosaria; Vielle, Anne; D'Adamo, Monica; Sbraccia, Paolo; Marini, Stefano; Borgiani, Paola; Coletta, Massimo; Novelli, Giuseppe

doi:10.1111/j.1399-0004.2008.01034.x

Cited by 17 publications

(12 citation statements)

References 59 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The latter values are consistent with an increase in osteoclast activity [Lombardi et al, 2008]. These biochemical markers did not substantially change over a period of almost 7 years.…”

supporting

confidence: 65%

Elbow deformities in a patient with mandibuloacral dysplasia type A

Guglielmi

D'Adamo

D’Apice

et al. 2010

American J of Med Genetics Pt A

View full text Add to dashboard Cite

Mandibuloacral dysplasia (MAD) is a rare autosomal recessive disorder characterized by postnatal growth retardation, craniofacial anomalies, mandibular hypoplasia with dental overcrowding, micrognathia and narrow nasal bridge and tip, skeletal anomalies (progressive osteolysis of the clavicles and distal phalanges, delayed closure of the cranial sutures, and joints contractures) and skin changes including mottled hyperpigmentation and atrophy. We and others have already reported lipodystrophy and metabolic complications associated with insulin resistance in patients affected with MAD [Novelli et al., 2002;Simha and Garg, 2002;Simha et al., 2003].Thus far, several mutations in LMNA gene have been reported in 23 patients (type A MAD-MADA) while only four patients have been reported with ZMPSTE24 mutations (type B MAD-MADB) [Shackleton et al., 2005;Agarwal et al., 2006]. The allelic heterogeneity of MADA patients is accompanied by phenotypic variability and expressivity, concerning appearance, age of onset, progression and severity degree of some clinical features.We describe elbow deformities in a previously characterized male 43-year-old patient, with homozygous LMNA missense mutation (R527H) [Novelli et al., 2002], who is the second oldest studied MADA patient [Kosho et al., 2007].The patient developed, over a period of nearly 2 years, deformation and swelling of the right elbow, associated with pain and nearly total loss of the joint function; in particular, the patient presented with elbow stiffness in slight flexion, severely limited articular excursion in both active and passive pronation and extension. The patient underwent both upper and lower limbs radiographs that showed osteolysis and destructive process of the right elbow and asymptomatic resorption of both femoral great trochanters more evident on the left one (Fig. 1). In particular, the right elbow showed joint space narrowing with loss of articular cartilage, humeral condyles dysplasia, erosion of both proximal ulna and radius, palmar angulation of ulnar olecranon resulting in arthrosic deformity with marked signs of hyperostosis and loss of normal articular contacts (Fig. 2). In a previous radiological assessment performed 3 years before, less extensive hyperostosis and condyles dysplasia was present with conserved articular contacts and no palmar angulation of ulna (Fig. 3A); a concurrent CT scan of the region enabled to show that these bone alterations were associated with intra-and peri-articular soft tissues edema (Fig. 3B). The monolateral appearance of the deformities could be explained, at least in part, by right handedness.Plasma calcium (9.2 mg/dl), phosphorus (3.9 mg/dl), and intact parathyroid hormone (55 pg/ml) concentrations were normal as well as plasma 25-OH vitamin D3 levels (27.6 ng/ml); plasma alkaline-phosphatase concentration and its bone isoenzyme were normal (respectively, 82 IU/L and 48%) whereas osteocalcin N-MID levels were low (10.94 pmol/L, normal range 14-42); on the contrary plasma osteoclast marker type-1 collagen C-te...

show abstract

“…The latter values are consistent with an increase in osteoclast activity [Lombardi et al, 2008]. These biochemical markers did not substantially change over a period of almost 7 years.…”

supporting

confidence: 65%

Elbow deformities in a patient with mandibuloacral dysplasia type A

Guglielmi

D'Adamo

D’Apice

et al. 2010

American J of Med Genetics Pt A

View full text Add to dashboard Cite

show abstract

“…9 (MMP-9) active form in serum sample such as in older patients (data not shown) [Lombardi et al, 2008]. The cases reported here indicate that MADA may be clinically manifest already in preschool children.…”

Section: Discussionmentioning

confidence: 87%

Mandibuloacral dysplasia type A in childhood

Garavelli

D’Apice

Rivieri

et al. 2009

American J of Med Genetics Pt A

View full text Add to dashboard Cite

Mandibuloacral dysplasia type A (MADA) is characterized by growth retardation, postnatal onset of craniofacial anomalies with mandibular hypoplasia, progressive acral osteolysis, and skin changes including mottled pigmentation, skin atrophy, and lipodystrophy. Owing to its slowly progressive course, the syndrome has been recognized in adults, and pediatric case reports are scarce. We present the clinical case of two children in whom the diagnosis of MADA was made at an unusually early age. A 5-year-old boy presented with ocular proptosis, thin nose, and short and bulbous distal phalanges of fingers. A 4-year-old girl presented with round face and chubby cheeks, thin nose, bulbous fingertips, and type A lipodystrophy. In both, a skeletal survey showed wormian bones, thin clavicles, short distal phalanges of fingers and toes with acro-osteolysis. Both children were found to be homozygous for the recurrent missense mutation, c.1580G>A, (p.R527H) in exon 9 of the LMNA gene. Thus, the phenotype of MADA can be manifest in preschool age; diagnosis may be suggested by short and bulbous fingertips, facial features, and lipodystrophy, supported by the finding of acral osteolysis, and confirmed by mutation analysis.

show abstract

“…Expression of a lamin A variant that causes mandibuloacral dysplasia type A and expression of unprocessed prelamin A in osteoblastlike cells lead to increased secretion of TGF- (47). MMP9 activity has also been reported to be elevated in serum from patients with mandibuloacral dysplasia type A (48). Even in normal tissues, there appears to be a general relationship between tissue stiffness, collagen expression, and lamin A expression (49).…”

Section: Ecm Is Altered In Dermal Fibroblasts From Patients With Lmnamentioning

confidence: 99%