Prenatal diagnosis of nail-patella syndrome

McIntosh, Iain; Clough, Mark V.; Gak, Eva; Frydman, Moshe

doi:10.1002/(sici)1097-0223(199903)19:3<287::aid-pd526>3.0.co;2-p

Cited by 13 publications

(4 citation statements)

References 6 publications

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“…11,42 Previous psychological evaluation of selfreport questionnaires revealed depression in five out of 10 cases and anxiety symptoms in five out of eight subjects, respectively. 42 In the present psychological assessment of 75 individuals, however, we found no evidence for psychological symptoms such as depression and mood symptoms associated with NPS.…”

Section: Discussionmentioning

confidence: 96%

Genotype–phenotype studies in nail-patella syndrome show that LMX1B mutation location is involved in the risk of developing nephropathy

et al. 2005

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Nail-patella syndrome (NPS) is characterized by developmental defects of dorsal limb structures, nephropathy, and glaucoma and is caused by heterozygous mutations in the LIM homeodomain transcription factor LMX1B. In order to identify possible genotype-phenotype correlations, we performed LMX1B mutation analysis and comprehensive investigations of limb, renal, ocular, and audiological characteristics in 106 subjects from 32 NPS families. Remarkable phenotypic variability at the individual, intrafamilial, and interfamilial level was observed for different NPS manifestations. Quantitative urinanalysis revealed proteinuria in 21.3% of individuals. Microalbuminuria was detected in 21.7% of subjects without overt proteinuria. Interestingly, nephropathy appeared significantly more frequent in females. A significant association was established between the presence of clinically relevant renal involvement in an NPS patient and a positive family history of nephropathy. We identified normal-tension glaucoma (NTG) and sensorineural hearing impairment as new symptoms associated with NPS. Sequencing of LMX1B revealed 18 different mutations, including six novel variants, in 28 families. Individuals with an LMX1B mutation located in the homeodomain showed significantly more frequent and higher values of proteinuria compared to subjects carrying mutations in the LIM domains. No clear genotype -phenotype association was apparent for extrarenal manifestations. This is the first study indicating that family history of nephropathy and mutation location might be important in precipitating individual risks for developing NPS renal disease. We suggest that the NPS phenotype is broader than previously described and that NTG and hearing impairment are part of NPS. Further studies on modifier factors are needed to understand the mechanisms underlying phenotypic heterogeneity.

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Section: Discussionmentioning

confidence: 96%

Genotype–phenotype studies in nail-patella syndrome show that LMX1B mutation location is involved in the risk of developing nephropathy

et al. 2005

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“…3 Preliminary evidence suggests that ADHD may be a constituent part of NPS, associated with the requirement for Lmx1b in the development of mesencephalic dopaminergic neurons (McIntosh et al, in preparation). 19,20 TrkA þ fibers are nociceptive sensory neurons with cell bodies located in the dorsal root ganglia and have axons that project into the dorsal laminae of the spinal cord (reviewed by Snider and McMahon 21 ). Although the migration of the TrkA afferents into the spinal cord of lmx1b À/À mice is abnormal, this deficit most likely reflects a noncell autonomous role of Lmx1b in the migration of the TrkA afferents since Lmx1b is not expressed in the dorsal root ganglion.…”

Section: Discussionmentioning

confidence: 99%

A neurological phenotype in nail patella syndrome (NPS) patients illuminated by studies of murine Lmx1b expression

Dunston

Reimschisel²,

Ding³

et al. 2004

Eur J Hum Genet

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Nail patella syndrome (NPS) is an autosomal dominant disorder affecting development of the limb, kidney and eye. NPS is the result of heterozygous loss-of-function mutations in the LIM-homeodomain transcription factor, LMX1B. Recent studies suggest that the NPS phenotype may be more extensive than recognized previously including neurologic and neurobehavioral aspects. To determine whether these findings correlated with the expression of Lmx1b during development, an internal ribosomal entry siteLacZ reporter was inserted into the 3 0 UTR of the endogenous murine gene. The pattern of Lmx1b expression during the development of the limb, eye and kidney correlates with the NPS phenotype. Additional sites of expression were observed in the central nervous system (CNS). The effects of the absence of Lmx1b in the CNS were determined in lmx1b À/À mice by histology and immunocytochemistry. Lmx1b is required for the differentiation and migration of neurons within the dorsal spinal cord. The inability of afferent sensory neurons to migrate into the dorsal horn is entirely consistent with diminished pain responses in NPS patients.

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“…used 5 DNA markers flanking the LMX1B locus to demonstrate that a fetus was affected with NPS. [ 6 ] Drut et al . observed renal changes in a spontaneously aborted 18-week fetus with NPS and proposed intrauterine kidney biopsy for the prenatal diagnosis.…”

Section: Discussionmentioning

confidence: 99%