A severe case of mandibuloacral dysplasia in a girl

Schrander-Stumpel, C. T. R. M.; Spaepen, Arthur; Fryns, Jean‐Pierre; Dumon, Jan E.

doi:10.1002/ajmg.1320430525

Cited by 29 publications

(26 citation statements)

References 6 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In humans, compound heterozygous mutations (p.F361fsX379 and p.W340R) in ZMPSTE24 have been described [Agarwal et al, 2003] in a case previously published as MAD with a progeroid appearance [Schrander-Stumpel et al, 1992]. The patient had overlapping symptoms of MAD and HGPS and died at the age of 24 years.…”

Section: Discussionmentioning

confidence: 96%

A homozygousZMPSTE24null mutation in combination with a heterozygous mutation in theLMNAgene causes Hutchinson-Gilford progeria syndrome (HGPS): insights into the pathophysiology of HGPS

et al. 2006

View full text Add to dashboard Cite

Hutchinson-Gilford progeria syndrome (HGPS) is a rare premature aging disorder normally caused by a spontaneous heterozygous mutation in the LMNA gene that codes for the nuclear lamina protein lamin A. Several enzymes are involved in the processing of its precursor, prelamin A, to the mature lamin A. A functional knockout of one of the enzymes involved in prelamin A processing, the zinc metalloprotease ZMPSTE24, causes an even more severe disorder with early neonatal death described as restrictive dermatopathy (RD). This work describes a HGPS patient with a combined defect of a homozygous loss-of-function mutation in the ZMPSTE24 gene and a heterozygous mutation in the LMNA gene that results in a C-terminal elongation of the final lamin A. Whereas the loss of function mutation of ZMPSTE24 normally results in lethal RD, the truncation of LMNA seems to be a salvage alteration alleviating the clinical picture to the HGPS phenotype. The mutations of our patient indicate that farnesylated prelamin A is the deleterious agent leading to the HGPS phenotype, which gives further insights into the pathophysiology of the disorder.

show abstract

Section: Discussionmentioning

confidence: 96%

A homozygousZMPSTE24null mutation in combination with a heterozygous mutation in theLMNAgene causes Hutchinson-Gilford progeria syndrome (HGPS): insights into the pathophysiology of HGPS

et al. 2006

View full text Add to dashboard Cite

show abstract

“…Our patient shared several features with those reported earlier in a patient with ZMPSTE24 mutations. 16 23 We therefore screened for mutations in this gene and identified compound heterozygous mutations. The first mutation, c.1085_1086insT in exon 9, has been reported previously in a patient with MADB 16 and results in a frameshift and premature protein truncation Phe361fsX379 (Leu362PhefsX19, according to standard mutation nomenclature guidelines at http://www.genomic.…”

Section: Mutation Analysismentioning

confidence: 99%

Compound heterozygous ZMPSTE24 mutations reduce prelamin A processing and result in a severe progeroid phenotype

Shackleton¹,

Smallwood²,

Clayton³

et al. 2005

Journal of Medical Genetics

108

View full text Add to dashboard Cite

“…Indeed, in a female patient with MAD, the clinical diagnosis of HSS has been suggested at the age of 2 years because of her characteristic facial appearance [Schrander-Stumpel et al, 1992]. HGPS is a rare progressive disorder characterized by extreme premature ageing.…”

mentioning

confidence: 99%

Hallermann-Streiff Syndrome: No Evidence for a Link to Laminopathies

Kortüm¹,

Chyrek²,

Fuchs³

et al. 2011

Mol Syndromol

View full text Add to dashboard Cite

ing from mutations in LMNA and ZMPSTE24 , respectively. ZMPSTE24 in addition to ICMT encode proteins involved in posttranslational processing of lamin A. We hypothesized that HSS is an allelic disorder to HGPS and MAD. As the nuclear shape is often irregular in patients with LMNA mutations, we first analyzed the nuclear morphology in skin fibroblasts of patients with HSS, but could not identify any abnormality. Sequencing of the genes LMNA, ZMPSTE24 and ICMT in the 8 patients with HSS revealed the heterozygous missense mutation c.1930C 1 T (p.R644C) in LMNA in 1 female. Extreme phenotypic diversity and low penetrance have been associated with the p.R644C mutation. In ZMPSTE24 and ICMT , no pathogenic sequence change was detected in patients with HSS. Together, we found no evidence that HSS is another laminopathy.

show abstract

A severe case of mandibuloacral dysplasia in a girl

Cited by 29 publications

References 6 publications

A homozygousZMPSTE24null mutation in combination with a heterozygous mutation in theLMNAgene causes Hutchinson-Gilford progeria syndrome (HGPS): insights into the pathophysiology of HGPS

A homozygousZMPSTE24null mutation in combination with a heterozygous mutation in theLMNAgene causes Hutchinson-Gilford progeria syndrome (HGPS): insights into the pathophysiology of HGPS

Compound heterozygous ZMPSTE24 mutations reduce prelamin A processing and result in a severe progeroid phenotype

Hallermann-Streiff Syndrome: No Evidence for a Link to Laminopathies

Contact Info

Product

Resources

About