Growth and skeletal development in families with NOGGIN gene mutations.
BACKGROUND
There is a scarcity of data on height as well as bone densitometry in humans with NOGGIN mutations.


METHODS
In 2 families with symphalangism, anthropometry, bone densitometry and genetic analysis of the NOGGIN gene were performed.


RESULTS
In family A, the height standard deviation scores of the affected father and son were -0.4 and 3.5, respectively. In family B, the height standard deviation scores of the affected father, twin daughters and another daughter were 1.7, 1.8, 2.4 and 1.8, respectively. In the children, percentage predicted bone mineral content (BMC) for height at the appendicular sites (total femur, femoral neck) was lower than at an axial site lumbar spine. In the 2 fathers, median bone mineral density at total femur and femoral neck was -0.3 standard deviation scores (-0.7, 0.2) and at lumbar spine the scores were -0.4 and 0.9. The children had median tibial and radial speed of sound velocities of -2.1 (-0.9 to -6.4) and -1.4 (-0.2 to -4.9), respectively. DNA analysis revealed a novel missense mutation in family A and family B, resulting in a Met190Val substitution and a Pro42Arg substitution, respectively.


CONCLUSIONS
Heterozygous gene mutations in NOGGIN are associated with tall stature in children but not necessarily in adults. The appendicular BMC and speed of sound may be low in affected children but normalises by adulthood. However, axial BMC seems normal in childhood and is high in adulthood.
Oxley
C D
CD
Department of Paediatric Endocrinology, Royal Hospital for Sick Children, Edinburgh, UK.
Rashid
R
R
Goudie
D R
DR
Stranks
G
G
Baty
D U
DU
Lam
W
W
Kelnar
C J
CJ
Ahmed
S F
SF
D000293:Adolescent; D000328:Adult; D001827:Body Height / Q000235:genetics*; D015519:Bone Density / Q000235:genetics; D001846:Bone Development / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D002648:Child; D005260:Female; D006801:Humans; D008297:Male; D020125:Mutation, Missense / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D013580:Synostosis / Q000235:genetics; D000099176:Noggin Protein
D002352:Carrier Proteins; D000099176:Noggin Protein