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Division of Nutrition and Metabolic Diseases, Center for Human Nutrition, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75390
Address all correspondence and requests for reprints to: Abhimanyu Garg, Division of Nutrition and Metabolic Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390-9052. E-mail: Abhimanyu.garg{at}utsouthwestern.edu
Abstract
Mandibuloacral dysplasia (MAD) is a rare autosomal recessive disorder that is characterized by mandibular and clavicular hypoplasia, acroosteolysis, delayed closure of cranial sutures, joint contractures, and mottled cutaneous pigmentation. It is also associated with partial lipodystrophy, but the pattern of fat loss has not been well characterized. We studied body fat distribution in two male and two female patients with MAD by anthropometry, dual energy x-ray absorptiometry, and magnetic resonance imaging. Blood glucose and insulin responses during an oral glucose tolerance test and fasting serum lipoproteins were determined. Three of the four subjects had loss of sc fat from the extremities with normal or slight excess in the neck and truncal regions (termed type A pattern). In contrast, one patient had generalized loss of sc fat involving the face, trunk, and extremities (type B pattern). All of the patients had normal glucose tolerance but had fasting and postprandial hyperinsulinemia suggestive of insulin resistance. Elevated serum triglycerides with low high-density lipoprotein cholesterol levels were noted in three subjects. We conclude that familial partial lipodystrophy associated with MAD presents with two types of body fat distribution patterns, both of which are associated with insulin resistance and its metabolic complications.
MANDIBULOACRAL DYSPLASIA (MAD) is a rare autosomal recessive disorder [Mendelian Inheritance in Man (MIM) no. 248370] that was first described by Young et al. and Sensenbrenner and Fiorelli in 1971 (1, 2). The characteristic features of this syndrome include postnatal growth retardation; craniofacial anomalies such as mandibular hypoplasia with dental overcrowding, bird-like facies with prominent eyes, and beaked nose; skeletal anomalies such as progressive osteolysis of the clavicles and terminal phalanges, delayed closure of the cranial sutures; and skin changes such as mottled hyperpigmentation of the trunk and atrophy over the hands and feet. Other features less commonly associated with this condition are hypogonadism or delayed puberty (2, 3, 4), bilateral sensory neural deafness (4, 5), alopecia (6, 7, 8), high arched palate, and cutaneous calcinosis (9, 10).
Lipodystrophy and metabolic complications associated with insulin resistance such as diabetes and hypertriglyceridemia have also been noted in some patients (5, 7, 11, 12). However, the pattern of fat loss in these patients has not been studied systematically and is not well characterized. The main purpose of this investigation, therefore, was to study distribution of adipose tissue in four patients with lipodystrophy associated with MAD by using anthropometry, dual energy x-ray absorptiometry (DEXA), and whole-body magnetic resonance imaging (MRI) similar to our previous studies with different types of genetic lipodystrophies (13, 14). Other aims were to describe the clinical features and to investigate metabolic abnormalities associated with insulin resistance in these four patients.
Patients and Methods
Patient 1
Patient MAD 100.3 is a 20-yr-old Hispanic female, the first child of healthy, unrelated parents. The pregnancy was uneventful; she was born prematurely at 32-wk gestation with a birth weight of 2.6 kg. She had normal growth and development during infancy and early childhood. The parents first noticed rounding of her fingertips at age 4–5 yr. She also developed progressive micrognathia. By age 10 yr, progressive loss of sc fat from the arms and legs was noted, which resulted in increased muscular appearance. At the same time, excess deposition of fat was noted in the face, neck, chest, and abdomen. She underwent surgical excision of osteochondroma of the right hip at age 12 yr. She attained menarche at age 13 yr and has had regular menstrual periods since. She underwent reconstructive surgery for receding chin besides a rhinoplasty at age 15 yr. She had overcrowded teeth, necessitating extractions of six teeth between the ages of 14–15 yr. She was diagnosed to have spinal cord compression at the level of the fifth cervical vertebra at age 17 yr, for which two vertebrae were removed and replaced by a bone graft from the hip. There was no evidence of a neoplasm in the excised vertebrae.
Physical examination revealed a height of 1.52 m and a weight of 43.5 kg. She had bird-like facies with prominent eyes, beaked nose, and a small mouth. Fingertips were rounded with marked resorption of all terminal phalanges, and flexion contractures of the fifth finger were noted bilaterally (Fig. 1
). The toes also had a clubbed appearance with resorption of the terminal phalanges. There was mottled hyperpigmentation over the trunk besides acanthosis nigricans in the axillae. The liver was palpable 7 cm below the right costal margin. Breast development was Tanner stage 5, and pubic hair was Tanner stage 4 with no clitoromegaly. Excessive hair was noted on the face, arms, and legs, but she had no axillary hair. There was no alopecia or premature graying. Subcutaneous fat was nearly absent from both the upper and lower extremities with prominent muscles and superficial veins (Fig. 1). Loss of sc fat was noted from the dorsum of the hands and feet with normal palmar and plantar fat. She had increased fat deposition over the neck and face and had a prominent dorsal cervical fat pad (buffalo hump) and double chin. Radiographs and MRI studies showed clavicular hypoplasia with lateral third of the clavicles deficient bilaterally, small mandibular rami, small cervical vertebral bodies, and lytic defects in the skull and lower third of the left femur.
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Patient MAD 100.4 is the 16-yr-old sister of the previously described patient. She was born at full term after an uneventful pregnancy with a birth weight of 3 kg. Rounding of the fingertips was noted at age 3–4 yr, and like her sister, she developed crowding of the teeth leading to dental extractions at age 8 yr. Loss of sc fat from the extremities was noticed by age 10 yr. She had breast development at age 11 yr and menarche at age 12 yr, but has had irregular menstrual periods. Physical examination revealed a height of 1.41 m and weight of 42 kg. She had similar dysmorphic features like her sister such as bird-like facies with prominent eyes and beaked nose, resorption of the terminal phalanges in the hands and feet, and mottled skin pigmentation. Hepatomegaly and acanthosis nigricans in the axillae were also present. Breast development was normal, and she had Tanner stage 4 pubic hair. Subcutaneous fat loss from the extremities was accompanied by increased fat over the supraclavicular area. Radiographs and MRI studies revealed hypoplasia of the clavicles and mandibles, acroosteolysis, small cervical vertebral bodies, and lucencies in the skull and femur. Routine laboratory tests revealed slightly elevated serum 
glutamyl transferase and alanine amino transferase levels.
Patient 3
Patient MAD 300.4 is a 12-yr-old white male of Italian descent who had an unremarkable birth and family history. Although his physical growth had been normal, he had autism and mental impairment. Postnatal dysmorphic features included acro-osteolysis (resorption of terminal phalanges), stiff joints, clavicular hypoplasia, and mandibular regression with dental overcrowding that necessitated tooth extractions. Progressive fat loss had been noted from the limbs, with excess fat around the face and in the submental region. His height was 1.33 m and weight 40.5 kg. Routine laboratory tests showed a slightly elevated serum alanine amino transferase level.
Patient 4
Patient MAD 400.5 is a 25-yr-old non-Hispanic white male, the third child of healthy, unrelated parents, born after an uncomplicated full-term pregnancy. His birth weight was 3.2 kg, and he had normal growth and development as a child. He had cryptorchidism, and at age 7 yr bilateral testicular biopsies revealed rudimentary testes with growth arrest of seminiferous tubules and markedly reduced spermatogonia. He had a normal male karyotype (46, XY) and underwent bilateral orchiectomy with placement of testicular prosthesis at the age of 8 yr. He has been receiving im T from age 10 yr (currently 300 mg T every 3 wk), but his muscle development and penile growth have been poor and his height (1.7 m) is less than that of his two normal male siblings (1.88 and 1.93 m). Besides the thin body habitus, he gradually developed facial abnormalities such as sunken cheeks, narrow flat nose, and small chin with crowded teeth for which he underwent reconstructive surgeries and dental extractions. Fat loss was first noticed from the arms and legs when he was about 9–10 yr old and has progressively involved the face and the rest of the body. By age 15 yr, he was diagnosed to have bilateral hearing loss due to inadequately formed auditory canals. He was being treated for hypertriglyceridemia from age 21 yr with 600 mg gemfibrozil twice daily.
Physical examination revealed body weight of 51.5 kg. He had a bird-like face with a beaked nose and receding chin, besides a high-pitched voice. There was no acroosteolysis, but his hands and feet were small. There was generalized loss of sc adipose tissue, including the palmar and plantar surfaces with calluses on the feet (Fig. 2). The skin also showed mottled hyperpigmentation over the lower trunk and upper thighs. There was no acanthosis nigricans or hepatomegaly. He had a microphallus (penile size of 2.5 cm), but body and facial hair distribution was normal.
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Patients 1, 2, and 4 were admitted to the General Clinical Research Center at University of Texas Southwestern Medical Center at Dallas for evaluation. Information on patient 3 was obtained by a questionnaire, telephone interview, and examination of his photographs. A written informed consent was obtained from all of the patients, and the study protocol was approved by the Institutional Review Board of University of Texas Southwestern Medical Center.
Anthropometric measurements. In subjects evaluated at Dallas, height and body weight were measured by standard procedures. Skinfold thickness was measured with a Lange caliper (Cambridge Scientific Industries, Cambridge, MD) at the chin, five truncal (chest, mid-axillary, abdominal, subscapular, and suprailiac), and six peripheral (biceps, triceps, forearm, hip, thigh, and calf) sites on the right side of the body. The mean of three repeat measurements at each site was calculated.
DEXA. Whole-body DEXA scan was performed with a multiple detector fan-beam Hologic QDR-2000 densitometer (Hologic, Inc., Waltham, MA). Data were obtained from the head, upper extremities, trunk, and lower extremities; the proportion of fat in individual regions as well as whole body was calculated as percentage of body mass. Data were also obtained for measurement of lean tissue mass and bone mineral density. Appendicular skeletal muscle mass was calculated as fat-free soft tissue in the upper and lower extremities, and total body skeletal muscle mass was estimated by dividing the appendicular skeletal muscle mass by 0.75 (15).
MRI. Whole-body MRI scan was performed on patients 1 and 2 with a 1.5 Tesla imaging device (Philips Medical Systems, Best, The Netherlands). The patients were evaluated using 10-mm-thick T1 imaging techniques with TR (repetition time) of 580 msec, TE (echo time) of 8 msec and a 384 x 512 matrix combined with a 45-cm field of view.
Blood samples. Blood was collected after a 12-h overnight fast for analysis of serum lipoproteins, insulin, leptin, glucose, and a chemistry profile. Blood samples from patient 3 were sent by overnight mail to the University of Texas Southwestern Medical Center for analysis.
Oral glucose tolerance test (OGTT). A standard OGTT with 75-g glucose was performed after a 12-h overnight fast. Venous blood was collected for determination of glucose and insulin concentrations at 30 min, 15 min, and immediately before glucose administration, and at 30-min intervals thereafter for 180 min.
Biochemical analyses. Plasma glucose was measured by the glucose oxidase method with a Beckman Coulter glucose analyzer (Beckman Coulter, Inc., Fullerton, CA). Plasma insulin and leptin levels were determined by RIA using commercial kits (Linco Research, Inc., St. Charles, MO). Fasting serum samples were analyzed for cholesterol and triglycerides by an enzymatic method using kits (Roche Molecular Biochemicals, Indianapolis, IN). Serum high-density lipoprotein (HDL) cholesterol was measured enzymatically after lipoproteins containing apolipoprotein B had been precipitated with phosphotungstic acid (16). Serum chemistry was measured as a part of the systematic multichannel analysis by a commercial laboratory (SmithKline Beecham Clinical Laboratories, Dallas, TX).
Results
The clinical features of all our patients are summarized in Table 1 in comparison with 34 previously reported cases (1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 17, 18, 19, 20, 21, 22, 23, 24, 25). The onset of symptoms was noticed in early childhood in our patients. All of our patients had micrognathia suggestive of mandibular hypoplasia, but only three of them had clavicular hypoplasia and acroosteolysis. Growth retardation and the characteristic bird-like facies were noticed in three of the four subjects, whereas mottled cutaneous pigmentation was seen in all of them. Joint stiffness and flexion contractures of the fifth finger were present in three patients. Other characteristic features of individual patients have been described earlier.
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shows the skinfold thickness in patients 1, 2, and 4. Both patients 1 and 2 had markedly reduced peripheral skinfold thickness compared with normal women, whereas the truncal skinfold measurements were in the normal range (26). Patient 4 had decreased skinfold thickness at both the peripheral and truncal sites compared with normal men (27).
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shows the regional and whole body adipose tissue distribution as estimated by DEXA scan. Compared with normal young women (28), patients 1 and 2 had decreased whole body fat, whereas the percentage body fat in patient 4 was comparable to normal young men (28). All of the three patients had less fat in the arms and legs compared with normal subjects, whereas truncal fat was within the normal range. Patients 1 and 2 seemed to have well preserved skeletal muscle mass, although it was low in patient 4. All three patients had decreased bone mineral density.
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and 5). Axial MRI sections through both the upper and lower extremities, as well as through the gluteal region, revealed an apparent excess of adipose tissue in the intermuscular fasciae. The sc truncal adipose tissue, both from the thoracic and abdominal areas, was less conspicuously reduced, and there was no apparent reduction of fat noted in the intra-abdominal and intrathoracic sites (Fig. 6). A slight excess of sc fat was also noted in the posterior cervical area (Fig. 7). Normal amounts of fat were noted in anatomic sites where mechanical adipose tissue is present, such as the orbits, palm, sole, scalp, and periarticular regions.
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shows the metabolic variables in all four patients. All of them had a normal fasting plasma glucose level but elevated fasting insulin levels. All three patients who underwent an OGTT (Fig. 8) had normal glucose tolerance but had a marked postprandial hyperinsulinemic response. The peak plasma insulin concentrations exceeded 1500 pmol/liter in all of them.
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Serum leptin levels were similar to those reported recently in race- and sex-matched adults, aged at least 20 yr, with a similar sum of skinfold thickness less than the 10th decile (30). The ratios of serum leptin levels to absolute fat mass were also comparable to previously reported values in studies using a similar leptin assay (31). The low leptin levels seen in our patients thus probably reflect reduced total body fat content.
Discussion
Our evaluation of body fat distribution in patients with familial partial lipodystrophy (FPL) associated with MAD using anthropometry, DEXA, and whole body MRI revealed two different patterns of loss of body fat, namely, types A and B. Type A pattern is characterized by fat loss from the extremities with normal or increased fat in the face, neck, and truncal region and was noted in patients 1, 2, and 3. Type B pattern is characterized by generalized loss of sc fat involving the face and truncal regions besides the extremities, as noted in patient 4. In previous reports of patients with MAD, some authors failed to mention lipodystrophy (3, 9, 24), whereas others made references to the loss of sc adipose tissue (11, 21, 22) but without a detailed description.
Skinfold thickness measurements in our patients 1 and 2 (Fig. 3
) clearly demonstrated fat loss from the extremities with sparing of the truncal regions. MRI and DEXA scan confirmed the same, the former also revealing the slight excess fat accumulation in the dorsal cervical region. Furthermore, the MRI studies revealed increased fat in the intermuscular fascial planes and normal amounts of intrathoracic and intra-abdominal adipose tissue. There was also no fat loss from the orbit, palm, sole, scalp, and periarticular regions where adipose tissue only serves a mechanical function. We are not aware of any previous reports describing adipose tissue distribution in MAD using MRI, but a similar pattern of body fat loss has been reported previously on physical examination of some patients, which supports our findings. For example, the patient described by Young et al. (1) had diminished fat over the distal extremities but increased fat over the abdomen and chest as well as in the face and neck region. Similarly, examination of the published pictures of the patient described by Sensenbrenner and Fiorili (2) revealed lack of sc fat with marked muscularity of both the upper and lower extremities. Particularly noticeable was loss of sc fat from the gluteal region. The authors noted an increase in sc tissue in a buffalo hump distribution over the back and neck. The patient also had a double chin appearance. Freidenberg et al. (5) reported progressive loss of sc fat from the extremities and trunk below the level of the nipples by the age of 16 yr in patient 1. Examination of this patient’s photographs (courtesy G. Freidenberg) confirmed lack of sc fat from the extremities and gluteal region and the presence of excess fat in the face and neck region, causing a double chin appearance. Similarly, examination of the pictures published by Pallota and Morgese (3) and by Tudisco et al. (24) reveals that both of these patients had marked paucity of sc fat in the extremities and had excess fat in the trunk and neck regions. This pattern of lipodystrophy is similar to that reported by us in patients with FPL, Dunnigan variety, who have loss of sc fat mainly from the extremities with excess fat in the face, neck, and truncal regions (14).
On the other hand, patient 4 had a more generalized loss of sc fat involving the face and truncal region besides the extremities as shown by the skinfold measurements (Fig. 3). Also remarkable was the absence of fat from the palms and soles. A similar pattern of fat loss has been noted in one of the patients (patient 3) reported by Freidenberg et al. (5) and subsequently by Ng and Stratakis (4). Examination of the photographs of patient 2 (courtesy G. Freidenberg) in the same case series (5) also revealed striking fat loss from the face besides the extremities. All of these patients appear to have thin limbs with decreased muscle mass as well. It is, however, not clear whether this is related to disuse atrophy from joint contractures or to the associated hypogonadism or whether it is a distinct feature of this syndrome. This type B pattern of FPL associated with MAD needs to be studied in greater detail.
Interestingly, both patterns of lipodystrophies are associated with insulin resistance and its metabolic sequelae. Although none of our patients had diabetes or impaired glucose tolerance, marked hyperinsulinemia during the fasting and postprandial states suggests moderate to severe insulin resistance. Diabetes has been reported previously in three male patients aged 16, 17, and 41 yr (5) and in a 14-yr-old female patient with this syndrome (11). Impaired glucose tolerance was observed in a 26-yr-old male and a 37-yr-old female patient (11). Furthermore, Cutler et al. (12) reported a marked reduction in insulin-stimulated glucose uptake on euglycemic hyperinsulinemic glucose clamp studies in two patients. Because insulin resistance in these patients occurred without obesity, excessive levels of counter regulatory hormones, or anti-insulin-receptor antibodies, the authors concluded that it was caused by the accompanying lipodystrophy (12).
Three of our patients had elevated serum triglycerides and low HDL-cholesterol levels, a lipid profile characteristic of insulin resistance. All of these metabolic derangements including insulin resistance, tendency for diabetes mellitus, and dyslipidemia may increase the risk of these patients to develop coronary artery disease. Indeed, the patient described initially by Cohen et al. (17), Freidenberg et al. (5), and most recently by Ng and Stratakis (4) had coronary artery bypass graft for extensive coronary artery disease at age 53 yr (McKusick, V., and E. Arioglu, personal communication).
MAD is not only a rare disorder, but also has protean manifestations, many of them overlapping with other progeroid syndromes. Patients with MAD have previously been described as having Werner syndrome (17), craniomandibular dermatodysostosis (9), hereditary sclerosing poikiloderma (19), and Hutchinson-Gilford progeria (21). The diagnostic confusion probably results from the many overlapping features between the various progeroid syndromes. The differential diagnosis of MAD and other progeroid syndromes has been discussed in sufficient detail by Esterly et al. (32). As shown in Table 1, our patients had most of the characteristic features associated with MAD. We have also observed decreased skeletal muscle mass in the type B pattern of lipodystrophy and decreased bone mineral density in three of our patients. Patient 4 did not have the typical clavicular hypoplasia and acroosteolysis. But these features were absent in some earlier case reports as well (4, 5, 10). His features closely resemble those described by Ng and Stratakis (4) in a 52-yr-old male who was previously described to have Werner syndrome (17). We had also considered the diagnosis of Werner syndrome in our patient, however, earlier onset of symptoms, the absence of cataracts or premature graying, and absence of mutations in the coding region of WRN gene (courtesy of Dr. J. Oshima, Seattle, WA) makes the possibility of Werner syndrome highly unlikely. Interestingly, like our patient, the patients described by Ng and Stratakis (4) and by Freidenberg et al. (5) also had hypogonadism, bilateral sensory-neural deafness, and type B pattern of lipodystrophy. It is possible that these patients manifest a variant form of the typical MAD syndrome. Undescended testis (22) and hypogonadotropic hypogonadism have been described in other patients with this syndrome (11). Identification of the genetic basis for MAD will probably help us in understanding the underlying molecular basis of various different phenotypes.
In summary, FPL associated with MAD may present with two types of body fat distribution patterns; type A pattern is characterized by fat loss from the extremities with normal or increased fat in the face, neck, and truncal region, whereas type B pattern is characterized by generalized loss of sc fat. Both types of lipodystrophies associated with MAD are associated with insulin resistance and its metabolic complications.
Acknowledgments
We are grateful to Drs. David Feinstein and Ravi Shankar for patient referral; Drs. Elizabeth Obialo and Dali Chen for assistance in patient evaluation; Dr. Paul Weatherall for help with MRI studies; and Angela Osborn, Jerri Payne, Brian Fox, and the nursing services of the General Clinical Research Center at University of Texas Southwestern Medical Center, Dallas, for their excellent technical support.
Footnotes
This study was supported in part by NIH Grants M01-RR00633 and R01-DK54387 and by the Southwestern Medical Foundation.
Abbreviations: DEXA, Dual energy x-ray absorptiometry; FPL, familial partial lipodystrophy; HDL, high-density lipoprotein; MAD, mandibuloacral dysplasia; MRI, magnetic resonance imaging or image; OGTT, oral glucose tolerance test.
Received September 6, 2001.
Accepted November 5, 2001.
References
This article has been cited by other articles:
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 |
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  S. Groh, H. Zong, M. M. Goddeeris, C. S. Lebakken, D. Venzke, J. E. Pessin, and K. P. Campbell Sarcoglycan Complex: IMPLICATIONS FOR METABOLIC DEFECTS IN MUSCULAR DYSTROPHIES J. Biol. Chem., July 17, 2009; 284(29): 19178 - 19182. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. K. Agarwal, I. Kazachkova, S. Ten, and A. Garg Severe Mandibuloacral Dysplasia-Associated Lipodystrophy and Progeria in a Young Girl with a Novel Homozygous Arg527Cys LMNA Mutation J. Clin. Endocrinol. Metab., December 1, 2008; 93(12): 4617 - 4623. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Lombardi, F. Gullotta, M. Columbaro, A. Filareto, M. D'Adamo, A. Vielle, V. Guglielmi, A. M. Nardone, V. Azzolini, E. Grosso, et al. Compound Heterozygosity for Mutations in LMNA in a Patient with a Myopathic and Lipodystrophic Mandibuloacral Dysplasia Type A Phenotype J. Clin. Endocrinol. Metab., November 1, 2007; 92(11): 4467 - 4471. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. A. Hegele, T. R. Joy, S. A. Al-Attar, and B. K. Rutt Thematic review series: Adipocyte Biology. Lipodystrophies: windows on adipose biology and metabolism J. Lipid Res., July 1, 2007; 48(7): 1433 - 1444. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. L. V. Broers, F. C. S. Ramaekers, G. Bonne, R. B. Yaou, and C. J. Hutchison Nuclear lamins: laminopathies and their role in premature ageing. Physiol Rev, July 1, 2006; 86(3): 967 - 1008. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Bakay, Z. Wang, G. Melcon, L. Schiltz, J. Xuan, P. Zhao, V. Sartorelli, J. Seo, E. Pegoraro, C. Angelini, et al. Nuclear envelope dystrophies show a transcriptional fingerprint suggesting disruption of Rb-MyoD pathways in muscle regeneration Brain, April 1, 2006; 129(4): 996 - 1013. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Filesi, F. Gullotta, G. Lattanzi, M. R. D'Apice, C. Capanni, A. M. Nardone, M. Columbaro, G. Scarano, E. Mattioli, P. Sabatelli, et al. Alterations of nuclear envelope and chromatin organization in mandibuloacral dysplasia, a rare form of laminopathy Physiol Genomics, October 17, 2005; 23(2): 150 - 158. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Garg, O. Cogulu, F. Ozkinay, H. Onay, and A. K. Agarwal A Novel Homozygous Ala529Val LMNA Mutation in Turkish Patients with Mandibuloacral Dysplasia J. Clin. Endocrinol. Metab., September 1, 2005; 90(9): 5259 - 5264. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S Shackleton, D T Smallwood, P Clayton, L C Wilson, A K Agarwal, A Garg, and R C Trembath Compound heterozygous ZMPSTE24 mutations reduce prelamin A processing and result in a severe progeroid phenotype J. Med. Genet., June 1, 2005; 42(6): e36 - e36. [Full Text] [PDF]
|
|
|
|
|
|
M Plasilova, C Chattopadhyay, P Pal, N A Schaub, S A Buechner, H. Mueller, P Miny, A Ghosh, and K Heinimann Homozygous missense mutation in the lamin A/C gene causes autosomal recessive Hutchinson-Gilford progeria syndrome J. Med. Genet., August 1, 2004; 41(8): 609 - 614. [Full Text] [PDF]
|
|
|
|
 |
|
 A. Garg Acquired and Inherited Lipodystrophies N. Engl. J. Med., March 18, 2004; 350(12): 1220 - 1234. [Full Text] [PDF]
|
|
|
|
|
|
J J Shen, C A Brown, J R Lupski, and L Potocki Mandibuloacral dysplasia caused by homozygosity for the R527H mutation in lamin A/C J. Med. Genet., November 1, 2003; 40(11): 854 - 857. [Full Text] [PDF]
|
|
|
|
 |
|
 A. K. Agarwal, J.-P. Fryns, R. J. Auchus, and A. Garg Zinc metalloproteinase, ZMPSTE24, is mutated in mandibuloacral dysplasia Hum. Mol. Genet., August 15, 2003; 12(16): 1995 - 2001. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Simha, A. K. Agarwal, E. A. Oral, J.-P. Fryns, and A. Garg Genetic and Phenotypic Heterogeneity in Patients with Mandibuloacral Dysplasia-Associated Lipodystrophy J. Clin. Endocrinol. Metab., June 1, 2003; 88(6): 2821 - 2824. [Abstract] [Full Text] [PDF]
|
|
|
|
|
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F. Caux, E. Dubosclard, O. Lascols, B. Buendia, O. Chazouilleres, A. Cohen, J.-C. Courvalin, L. Laroche, J. Capeau, C. Vigouroux, et al. A New Clinical Condition Linked to a Novel Mutation in Lamins A and C with Generalized Lipoatrophy, Insulin-Resistant Diabetes, Disseminated Leukomelanodermic Papules, Liver Steatosis, and Cardiomyopathy J. Clin. Endocrinol. Metab., March 1, 2003; 88(3): 1006 - 1013. [Abstract] [Full Text] [PDF]
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), and 4 (
).