Hypochondroplasia and Acanthosis nigricans: a new syndrome due to the p.Lys650Thr mutation in the fibroblast growth factor receptor 3 gene?
BACKGROUND
Hypochondroplasia (HCH) is a skeletal dysplasia inherited in an autosomal dominant manner due, in most cases, to mutations in the fibroblast growth factor receptor 3 (FGFR3). Acanthosis nigricans (AN) is a velvety and papillomatous pigmented hyperkeratosis of the skin, which has been recognized in some genetic disorders more severe than HCH involving the FGFR3 gene.


OBJECTIVE
After initial study of the proband, who had been consulted for short stature and who also presented AN, the study was extended to the patient's mother and to 12 additional family members.


METHODS
Clinical, biochemical and radiological studies were performed on the family. In addition, exons 11 and 13 of FGFR3 were analyzed.


RESULTS
The proband and ten relatives presented HCH plus AN and the analysis of FGFR3 showed the p.Lys650Thr mutation. The members with normal phenotypes were non-carriers of the mutation.


CONCLUSIONS
This is the first report of a large pedigree with the clinical phenotype of HCH plus AN due to a FGFR3 mutation, p.Lys650Thr. This finding demonstrates the coexistence of both conditions due to the same mutation and it might represent a true complex, which should be further established by searching for AN in mild HCH patients or for HCH in patients with AN.
Castro-Feijóo
Lidia
L
Unidad de Endocrinología Pediátrica, Crecimiento y Adolescencia, Departamento de Pediatría, Hospital Clínico Universitario y Universidad de Santiago de Compostela, 15706 Santiago de Compostela, Spain.
Loidi
Lourdes
L
Vidal
Anxo
A
Parajes
Silvia
S
Rosón
Elena
E
Alvarez
Ana
A
Cabanas
Paloma
P
Barreiro
Jesús
J
Alonso
Adela
A
Domínguez
Fernando
F
Pombo
Manuel
M
D000052:Acanthosis Nigricans / Q000150:complications* / Q000235:genetics*; D000293:Adolescent; D019943:Amino Acid Substitution / Q000235:genetics; D001483:Base Sequence; D001827:Body Height / Q000235:genetics; D004252:DNA Mutational Analysis; D006801:Humans; D008239:Lysine / Q000235:genetics; D008297:Male; D020125:Mutation, Missense / Q000502:physiology; D010009:Osteochondrodysplasias / Q000150:complications* / Q000235:genetics*; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000235:genetics*; D013577:Syndrome; D013912:Threonine / Q000235:genetics
D013912:Threonine; C496365:FGFR3 protein, human; D051498:Receptor, Fibroblast Growth Factor, Type 3; D008239:Lysine