Identification of a novel LRRK1 mutation in a family with osteosclerotic metaphyseal dysplasia.
Osteosclerotic metaphyseal dysplasia (OSMD) is a rare skeletal dysplasia characterized by osteosclerotic metaphyses with osteopenic diaphyses of the long tubular bones. Our previous study identified a homozygous elongation mutation in leucine-rich repeat kinase 1 gene (LRRK1) in a patient with OSMD and showed that Lrrk1 knockout mice exhibited phenotypic similarity with OSMD. Here we report a second LRRK1 mutation in Indian sibs with OSMD. They had homozygous mutation (c.5971_5972insG) that produces an elongated mutant protein (p.A1991Gfs*31) similar to the first case. The sibs had normal stature, normal intelligence and recurrent fractures. The common radiographic feature was asymmetric and variable sclerosis of vertebral end plates, pelvic margin and metaphyses of tubular bones. One of the sibs had facial dysmorphisms, dentine abnormalities and acro-osteolysis. A comparison between the three OSMD cases with LRRK1 mutations with different ages suggested that the sclerotic lesions resolved with age. Our findings further support that LRRK1 would cause a subset of OSMD cases.
Laboratory for Bone and Joint Diseases, RIKEN Center for Integrative Medical Sciences, Tokyo, Japan.
Long
L
Guo
Department of Medical Genetics, Kasturba Medical College, Manipal University, Manipal, India.
Katta M
KM
Girisha
Laboratory for Bone and Joint Diseases, RIKEN Center for Integrative Medical Sciences, Tokyo, Japan.
Aritoshi
A
Iida
Department of Medical Genetics, Kasturba Medical College, Manipal University, Manipal, India.
Malavika
M
Hebbar
Department of Medical Genetics, Kasturba Medical College, Manipal University, Manipal, India.
Anju
A
Shukla
Pediatric Orthopedic Services, Department of Orthopedics, Kasturba Medical College, Manipal University, Manipal, India.
Hitesh
H
Shah
Department of Pediatric Imaging, Tokyo Metropolitan Children's Medical Center, Fuchu, Japan.
Gen
G
Nishimura
Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
Naomichi
N
Matsumoto
Department of Pediatrics, Kasturba Medical College, Mangalore, Manipal University, Manipal, India.
Shifa
S
Nismath
Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
Noriko
N
Miyake
Laboratory for Bone and Joint Diseases, RIKEN Center for Integrative Medical Sciences, Tokyo, Japan.
Shiro
S
Ikegawa
D030981:Acro-Osteolysis / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D000293:Adolescent; D000328:Adult; D005260:Female; D050723:Fractures, Bone / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D015870:Gene Expression; D006720:Homozygote; D006801:Humans; D007194:India; D008297:Male; D009154:Mutation; D010009:Osteochondrodysplasias / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D010026:Osteosclerosis / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012008:Recurrence; D035781:Siblings; D013131:Spine / Q000378:metabolism / Q000473:pathology
C510751:LRRK1 protein, human; D017346:Protein Serine-Threonine Kinases