A novel compound heterozygous mutation in the DAP12 gene in a patient with Nasu-Hakola disease.
A 34-year-old woman showed clinical features characteristic of Nasu-Hakola disease (NHD), also designated polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL). The genetic analysis of the DAP12 gene (TYROBP) identified two heterozygous mutations composed of a previously reported single base deletion of 141G (141delG) in exon 3 and a novel single base substitution of G262T in exon 4, both of which are located on separate alleles. The protein sequence motif search indicated that both mutations encode truncated nonfunctional DAP12 polypeptides. This is the first case of NHD caused by compound heterozygosity for loss-of-function mutations in DAP12.
Kuroda
Ryo
R
Department of Neurology, Shizuoka Institute of Epilepsy and Neurological Disorders, 886 Urushiyama, Aoi-ku, Shizuoka 420-8688, Japan. ryou.kuroda@hospital.yaizu.shizuoka.jp
Satoh
Junichi
J
Yamamura
Takashi
T
Anezaki
Toshiharu
T
Terada
Tatsuhiro
T
Yamazaki
Kinya
K
Obi
Tomokazu
T
Mizoguchi
Kouichi
K
D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D001845:Bone Cysts / Q000150:complications / Q000235:genetics* / Q000473:pathology; D001927:Brain Diseases / Q000150:complications / Q000235:genetics* / Q000473:pathology; D004252:DNA Mutational Analysis / Q000379:methods; D005091:Exons; D005260:Female; D018698:Glutamic Acid / Q000235:genetics; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D009154:Mutation; D010009:Osteochondrodysplasias / Q000150:complications / Q000235:genetics* / Q000473:pathology; D011971:Receptors, Immunologic / Q000235:genetics*
D048868:Adaptor Proteins, Signal Transducing; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D011971:Receptors, Immunologic; C110546:TYROBP protein, human; D018698:Glutamic Acid