IL1RAPL1 is associated with mental retardation in patients with complex glycerol kinase deficiency who have deletions extending telomeric of DAX1.
IL1RAPL1 (interleukin-1 receptor accessory protein-like, gene 1) has recently been shown to be mutated in patients with X-linked mental retardation. Clinical experience has suggested that patients with the contiguous gene syndrome, complex glycerol kinase deficiency (cGKD), will have mental retardation (MR) if they have deletions extending from the GK gene into the DMD gene and/or involving a significant extension telomeric from DAX1. We examined cell lines from patients with cGKD whose clinical features would be informative and would allow us to determine if IL1RAPL1 deletions can help to explain the MR in patients with deletions extending telomeric from DAX1. Our results showed that nearly all patients with deletions involving DAX1, but not DMD, had MR if IL1RAPL1 was deleted. If ILIRAPLI and DMD were intact, the patients with DAX1 deletions only rarely had normal development. Deletions in DNA from patients with cGKD who exhibited MR and had normal IL1RAPL1 all involved the GK and DMD genes. Our data are consistent with the association of IL1RAPL1 gene deletion and MR in the majority of patients with cGKD and deletions extending telomeric from DAX1.
Zhang
Yao-Hua
YH
Department of Pediatrics, UCLA School of Medicine, Los Angeles, California 90095-7088, USA.
Huang
Bing-Ling
BL
Niakan
Kathy K
KK
McCabe
Linda L
LL
McCabe
Edward R B
ER
Dipple
Katrina M
KM
D000311:Adrenal Glands / Q000002:abnormalities; D002648:Child; D057137:DAX-1 Orphan Nuclear Receptor; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics*; D002658:Developmental Disabilities / Q000235:genetics; D016189:Dystrophin / Q000172:deficiency / Q000235:genetics; D023061:Gene Order; D040181:Genetic Diseases, X-Linked / Q000235:genetics*; D005991:Glycerol Kinase / Q000172:deficiency* / Q000235:genetics; D006801:Humans; D053577:Interleukin-1 Receptor Accessory Protein; D038901:X-Linked Intellectual Disability / Q000235:genetics*; D017472:Receptors, Interleukin-1 / Q000172:deficiency / Q000235:genetics* / Q000502:physiology; D018168:Receptors, Retinoic Acid / Q000172:deficiency / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics*; D017384:Sequence Deletion; D013577:Syndrome
D057137:DAX-1 Orphan Nuclear Receptor; C484258:DMD protein, human; D004268:DNA-Binding Proteins; D016189:Dystrophin; C407643:IL1RAPL1 protein, human; D053577:Interleukin-1 Receptor Accessory Protein; C539965:NR0B1 protein, human; D017472:Receptors, Interleukin-1; D018168:Receptors, Retinoic Acid; D012097:Repressor Proteins; D005991:Glycerol Kinase