Severe neuronopathic autosomal recessive osteopetrosis due to homozygous deletions affecting OSTM1.
Bone
; 55(2): 292-7, 2013 Aug.
Article
in En
| MEDLINE
| ID: mdl-23685543
ABSTRACT
Autosomal recessive osteopetrosis (ARO, MIM 259700) is a genetically heterogeneous rare skeletal disorder characterized by failure of osteoclast resorption leading to pathologically increased bone density, bone marrow failure, and fractures. In the neuronopathic form neurological complications are especially severe and progressive. An early identification of the underlying genetic defect is imperative for assessment of prognosis and treatment by hematopoietic stem cell transplantation. Here we describe for the first time homozygous microdeletions of different sizes affecting the OSTM1 gene in two unrelated consanguineous families with children suffering from neuronopathic infantile malignant osteopetrosis. Patients showed an exceptionally severe phenotype with variable CNS malformations, seizures, blindness, and deafness. Multi-organ failure due to sepsis led to early death between six weeks and five months of age in spite of intensive care treatment. Analysis of the breakpoints revealed different mechanisms underlying both rearrangements. Microdeletions seem to represent a considerable portion of OSTM1 mutations and should therefore be included in a sufficient diagnostic screening.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Osteopetrosis
/
Gene Deletion
/
Ubiquitin-Protein Ligases
/
Membrane Proteins
Type of study:
Prognostic_studies
Limits:
Female
/
Humans
/
Infant
/
Male
/
Newborn
Language:
En
Journal:
Bone
Journal subject:
METABOLISMO
/
ORTOPEDIA
Year:
2013
Document type:
Article
Affiliation country:
Germany