title: 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.
abstract: Uniparental disomy (UPD) is defined as the presence of a chromosome pair that derives from only one parent in a diploid individual. The human TRKA gene on chromosome 1q21-q22 encodes a receptor tyrosine kinase for nerve growth factor and is responsible for an autosomal recessive genetic disorder: congenital insensitivity to pain with anhidrosis (CIPA). We report here the second case of paternal UPD for chromosome 1 in a male patient with CIPA who developed normally at term and did not show overt dysmorphisms or malformations. 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 analyses of whole chromosome 1 revealed that the chromosome pair was exclusively derived from his father. Non-maternity was excluded by analyses of autosomes other than chromosome 1. Thus, we have identified a complete paternal isodisomy for chromosome 1 as the cause of reduction to homozygosity of the TRKA gene mutation, leading to CIPA. Our findings further support the idea that there are no paternally imprinted genes on chromosome 1 with a major effect on phenotype. UPD must be considered as a rare but possible cause of autosomal recessive disorders when conducting genetic testing.
authors.affiliation: Department of Pediatrics, Kumamoto University School of Medicine, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Miura
authors.forename: M
authors.initials: M
authors.lastname: Hiura
authors.forename: K
authors.initials: K
authors.lastname: Torigoe
authors.forename: O
authors.initials: O
authors.lastname: Numata
authors.forename: A
authors.initials: A
authors.lastname: Kuwahara
authors.forename: M
authors.initials: M
authors.lastname: Matsunaga
authors.forename: S
authors.initials: S
authors.lastname: Hasegawa
authors.forename: N
authors.initials: N
authors.lastname: Boku
authors.forename: H
authors.initials: H
authors.lastname: Ino
authors.forename: S
authors.initials: S
authors.lastname: Mardy
authors.forename: F
authors.initials: F
authors.lastname: Endo
authors.forename: I
authors.initials: I
authors.lastname: Matsuda
authors.forename: Y
authors.initials: Y
authors.lastname: Indo
mesh_terms: D000483:Alleles; D000782:Aneuploidy; D002675:Child, Preschool; D002878:Chromosomes, Human, Pair 1; D005220:Fathers; D005260:Female; D006239:Haplotypes; D006801:Humans; D007007:Hypohidrosis / Q000235:genetics*; D008297:Male; D009154:Mutation; D000699:Pain Insensitivity, Congenital / Q000235:genetics*; D010375:Pedigree; D016133:Polymerase Chain Reaction; D020917:Receptor, trkA / Q000235:genetics*
chemical_list: D020917:Receptor, trkA