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- ATR-X, α thalassaemia/mental retardation, X linked
- CNS, central nervous system
- ERCC6, excision repair cross complementing rodent repair deficiency, complementation group 6
- PCR, polymerase chain reaction
- SIOD, Schimke immuno-osseous dysplasia
- SMARCAL1, SWI/SNF2 related, matrix associated, actin dependent regulator of chromatin, subfamily a-like 1
- SMARCB1, swi/snf related matrix associated actin dependent regulator of chromatin subfamily b member 1
- SNF2, sucrose non-fermenting yeast homologue 2
Schimke immuno-osseous dysplasia (SIOD) is characterised by autosomal recessive inheritance, spondyloepiphyseal dysplasia causing growth retardation, defective cellular immunity, progressive nephropathy leading to renal failure, hyperpigmented macules, and dysmorphic facial features.1–16 Half of SIOD patients also have hypothyroidism, half episodic cerebral ischaemia, and a tenth bone marrow failure.3
SIOD is caused by mutations in SMARCAL1 (SWI/SNF2 related, matrix associated, actin dependent regulator of chromatin, subfamily a-like 1).17 SNF2 related proteins participate in the DNA nucleosome restructuring which commonly occurs during gene regulation and DNA replication, recombination, methylation, and repair.18,19
Generally SIOD patients surviving past 15-16 years have milder and fewer symptoms than patients dying at younger ages. These older patients do not suffer from hypothyroidism, recurrent infections, bone marrow failure, or central nervous system symptoms such as migraine headaches, transient ischaemic attacks, or strokes but do have spondyloepiphyseal dysplasia, renal disease, and T cell deficiency.3 These older patients have had two SMARCAL1 alleles with missense mutations, whereas most patients dying at younger ages have had at least one null allele.17 Based on this, we had hypothesised that patients surviving into adulthood have two hypomorphic alleles of SMARCAL1 as opposed to null alleles.
Here we review the longevity of 38 patients and the causes of death for 22 patients on whom we have collected detailed clinical data. We also describe a 20 year old woman who has had severe clinical symptoms of SIOD and has two SMARCAL1 null alleles; this suggests that prolonged survival of severely affected patients with SMARCAL1 null alleles is possible.
SUBJECTS AND METHODS
Patients referred to this study gave informed consent approved by the Institutional Review Board of Baylor College of Medicine (Houston, TX, USA) or the Hospital for Sick Children (Toronto, ON, Canada). We isolated DNA from peripheral blood. Clinical data, collected …
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