c.194 A>C (Q65P) mutation in the LMX1B gene in patients with nail-patella syndrome associated with glaucoma

[摘要] Purpose: To report the clinical,ophthalmic, extraophthalmic, and genetic characteristics ofnail-patella syndrome (NPS) in a Chilean family and to investigate theexpressivity of open angle glaucoma (OAG) and ocular hypertension (OHT)in the family members. Methods: Five family members affectedwith NPS and two unaffected members underwent a complete ophthalmologicexamination, including computerized visual field, optical coherencetomography (OCT) of the optic disc and ultrasound pachymetry. Renalfunction was assessed by urinalysis and blood tests. Orthopedicevaluations were also performed, including radiological studies of thewrist, elbow and hip joints. Genomic DNA was extracted from peripheralleukocytes of the five affected and two unaffected family members.Exons 2–6 of the LIM homeobox transcription factor 1-beta (LMX1B)genewere screened for mutations by DNA sequencing of the proband. Wealso screened for mutations in exon 2 by polymerase chainreaction-restriction fragment length polymorphism (PCR-RFLP) of theother participants and 91 blood donors. Results: Five living family members fromthree generations were positively diagnosed with NPS, three of themwith varying degrees of OAG and one with OHT. Retinal nervefiber layer (RNFL) thickness measured by spectral domain OCT was belownormal values in three individuals. All subjects evaluated had normalnephrologic function. Orthopedic, clinical, and radiologicalalterations were compatible with NPS. Screening for mutations in exons2- 6 of LMX1B showed a heterozygous missense mutation c.194A>C changing glutamine to proline within exon 2 in codon 65 (Q65P)of the coding sequence. This mutation was present in all NPS subjectsand absent in the unaffected family members and in 91 Chilean blooddonors. Conclusions: This is the first report ofc.194 A>C mutation in LMX1B in a Chilean family with NPS andthe second worldwide. The phenotype associated with this mutation isvariable within the family, although we noted a close connectionbetween the presence of the c.194 A>C mutation and the presence ofOHT or OAG and probably also with an early onset of OHT in patientswith NPS. All subjects older than 21 years had either OHT or OAG. Wealso suggest that the LMX1B mutation may be related toaffective disorders.

[学科分类] 生物化学/生物物理