Phenotype-genotype correlation in two patients with 12q proximal deletion.
Proximal 12q deletion is a very rare chromosomal abnormality. Only five cases have been reported. Among the five, an Argentinian patient (Case 1) with del(12)(q11q13) and a Japanese patient (Case 2) with del(12)(q12q13.12) were analyzed because they shared several clinical features: growth and psychomotor developmental delay; strabismus; broad and short nose with anteverted nostrils; high, arched palate; large, lowset ears; widely set nipples; short fingers and clinodactyly of fifth fingers; and abnormality of the second and third toes. To clarify the correlation between the deleted genes and their phenotypes, we delimited their deleted regions by fluorescence in situ hybridization (FISH). The overlapped region in the deletions spanned 6.2 Mb where at least 15 genes were predicted to localize on the current human genome database. Among them, YAF2 and AMIGO2 were the most plausible candidates to affect growth and psychomotor retardation, respectively, in both cases. Regarding unique symptoms in each case, congenital fibrosis of the extraocular muscles found only in Case 1 may be caused by KIF21A deletion and hearing loss and cleft palate in Case 2 by COL2A1 defect.
Miyake
Noriko
N
Department of Human Genetics, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan.
Tonoki
Hidefumi
H
Gallego
Marta
M
Harada
Naoki
N
Shimokawa
Osamu
O
Yoshiura
Koh-ichiro
K
Ohta
Tohru
T
Kishino
Tatsuya
T
Niikawa
Norio
N
Matsumoto
Naomichi
N
D000015:Abnormalities, Multiple / Q000235:genetics* / Q000473:pathology; D002675:Child, Preschool; D002872:Chromosome Deletion; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics*; D002972:Cleft Palate / Q000473:pathology; D024043:Collagen Type II / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D005838:Genotype; D034381:Hearing Loss / Q000473:pathology; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D007223:Infant; D008607:Intellectual Disability / Q000473:pathology; D016547:Kinesins / Q000235:genetics; D009124:Muscle Proteins / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics; D010641:Phenotype; D012097:Repressor Proteins / Q000235:genetics
C499177:COL2A1 protein, human; D024043:Collagen Type II; D004268:DNA-Binding Proteins; C119023:KIF21A protein, human; C485598:Kif21a protein, mouse; D009124:Muscle Proteins; D009419:Nerve Tissue Proteins; D012097:Repressor Proteins; C104531:YAF2 protein, human; C484486:Yaf2 protein, mouse; D016547:Kinesins