Retinoblastoma and hypochondroplasia: a case report of two germline mutations arising simultaneously.
OBJECTIVE
To report a rare case of a patient with two germline mutations arising de novo resulting in bilateral retinoblastoma and hypochondroplasia.


METHODS
A brief review about retinoblastoma and hypochondroplasia; a case report with genetic mutational analysis results.


METHODS
We report a patient manifesting the clinical features of both bilateral retinoblastoma and hypochondroplasia. Genetic analysis revealed two germline mutations, a seven base-pair deletion in exon 12 (G70313-703129del) in one allele of the retinoblastoma gene (RB1) and the N540K (C1620C > A) mutation in one allele of the fibroblast growth factor 3 (FGFR3) gene, a frequent mutation in hypochondroplasia. Neither parent has a personal or family history of cancer or ocular tumors. Only the patient's mother is short in stature, and her genetic analysis revealed no FGFR3 mutations.


CONCLUSIONS
Although the probability of both germline mutations occurring in a single individual is exceedingly low, the etiology and mechanism are unknown in this patient. To the best of our knowledge, this is the first report of two clinically distinct heritable germline mutations arising de novo in an individual.
Tsai
Tony
T
Ocular Oncology Division, Department of Ophthalmology, University of California-San Francisco, UCSF Medical Center, 10 Koret Way, San Francisco, CA 94143, U.S.A.
Gombos
Dan
D
Fulton
Lilia
L
Conway
Robert M
RM
O'Brien
Joan M
JM
Cronin
John E
JE
Muthialu
Arpitha
A
D005260:Female; D018095:Germ-Line Mutation / Q000235:genetics*; D006801:Humans; D007223:Infant; D010009:Osteochondrodysplasias / Q000235:genetics* / Q000473:pathology; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D051498:Receptor, Fibroblast Growth Factor, Type 3; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics*; D019572:Retinal Neoplasms / Q000235:genetics* / Q000473:pathology; D012175:Retinoblastoma / Q000235:genetics* / Q000473:pathology
D017468:Receptors, Fibroblast Growth Factor; C496365:FGFR3 protein, human; D011505:Protein-Tyrosine Kinases; D051498:Receptor, Fibroblast Growth Factor, Type 3