Complete paternal uniparental isodisomy for chromosome 1 revealed by mutation analyses of the TRKA (NTRK1) gene encoding a receptor tyrosine kinase for nerve growth factor in a patient with congenital insensitivity to pain with anhidrosis

Citation
Y. Miura et al., Complete paternal uniparental isodisomy for chromosome 1 revealed by mutation analyses of the TRKA (NTRK1) gene encoding a receptor tyrosine kinase for nerve growth factor in a patient with congenital insensitivity to pain with anhidrosis, HUM GENET, 107(3), 2000, pp. 205-209
Citations number
20
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Molecular Biology & Genetics
Journal title
HUMAN GENETICS
ISSN journal
0340-6717 → ACNP
Volume
107
Issue
3
Year of publication
2000
Pages
205 - 209
Database
ISI
SICI code
0340-6717(200009)107:3<205:CPUIFC>2.0.ZU;2-7
Abstract
Uniparental disomy (UPD) is defined as the presence of a chromosome pair th at derives from only one parent in a diploid individual. The human TRKA gen e on chromosome 1q21-q22 encodes a receptor tyrosine kinase for nerve growt h factor and is responsible for an autosomal recessive genetic disorder: co ngenital insensitivity to pain with anhidrosis (CIPA). We report here the s econd case of paternal UPD for chromosome 1 in a male patient with CIPA who developed normally at term and did not show oven dysmorphisms or malformat ions. He had only the usual features of CIPA with a homozygous mutation at the TRKA locus and a normal karyotype with no visible deletions or evidence of monosomy 1. Haplotype analysis of the TRKA locus and allelotype analyse s of whole chromosome 1 revealed that the chromosome pair was exclusively d erived from his father. Non-maternity was excluded by analyses of autosomes other than chromosome 1. Thus, we have identified a complete paternal isod isomy for chromosome 1 as the cause of reduction to homozygosity of the TRK A gene mutation, leading to CIPA. Our findings further support the idea tha t there are no paternally imprinted genes on chromosome 1 with a major effe ct on phenotype. UPD must be considered as a rare but possible cause of aut osomal recessive disorders when conducting genetic testing.