TC II deficiency: avoidance of false-negative molecular genetics by RNA-based investigations.
Transcobalamin II (TC II) is a plasma transport protein for cobalamin. TC II deficiency can lead to infant megaloblastic anemia, failure to thrive and to neurological complications. This report describes the genetic work-up of three patients who presented in early infancy. Initially, genomic investigations did not reveal the definite genetic diagnosis in the two index patients. However, analysis of cDNA from skin fibroblasts revealed a homozygous deletion of exon 7 of the TC II gene caused by the mutation c.940+303_c.1106+746del2152insCTGG (r.941_1105del; p.fs326X) in one patient. The other patients were siblings and both affected by an insertion of 87 bp on the transcript which was caused by the homozygous mutation c.580+624A>T (r.580ins87; p.fs209X). Additional experiments showed that cDNA from lymphocytes could have been used also for the genetic work-up. This report shows that the use of cDNA from skin fibroblasts or peripheral lymphocytes facilitates genetic investigations of suspected TC II deficiency and helps to avoid false-negative DNA analysis.
Universitätsklinikum Münster, Klinik und Poliklinik für Kinder- und Jugendmedizin, Münster, Germany. johannes.haeberle@kispi.uzh.ch
Johannes
J
Häberle
Silke
S
Pauli
Christoph
C
Berning
Hans G
HG
Koch
Michael
M
Linnebank
D000749:Anemia, Megaloblastic / Q000175:diagnosis* / Q000235:genetics; D002648:Child; D018076:DNA, Complementary / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D005500:Follow-Up Studies; D006801:Humans; D007231:Infant, Newborn; D008214:Lymphocytes / Q000378:metabolism; D008297:Male; D011379:Prognosis; D012313:RNA / Q000235:genetics* / Q000378:metabolism; D012867:Skin / Q000166:cytology / Q000378:metabolism; D014155:Transcobalamins / Q000172:deficiency* / Q000235:genetics*
D018076:DNA, Complementary; D014155:Transcobalamins; D012313:RNA