Language:
English
In:
American journal of human genetics, 2014-12-04, Vol.95 (6), p.763-770
Description:
Catel-Manzke syndrome is characterized by Pierre Robin sequence and a unique form of bilateral hyperphalangy causing a clinodactyly of the index finger. We describe the identification of homozygous and compound heterozygous mutations in TGDS in seven unrelated individuals with typical Catel-Manzke syndrome by exome sequencing. Six different TGDS mutations were detected: c.892A〉G (p.Asn298Asp), c.270_271del (p.Lys91Asnfs∗22), c.298G〉T (p.Ala100Ser), c.294T〉G (p.Phe98Leu), c.269A〉G (p.Glu90Gly), and c.700T〉C (p.Tyr234His), all predicted to be disease causing. By using haplotype reconstruction we showed that the mutation c.298G〉T is probably a founder mutation. Due to the spectrum of the amino acid changes, we suggest that loss of function in TGDS is the underlying mechanism of Catel-Manzke syndrome. TGDS (dTDP-D-glucose 4,6-dehydrogenase) is a conserved protein belonging to the SDR family and probably plays a role in nucleotide sugar metabolism.
Subject(s):
Adolescent ; Adult ; Amino Acid Sequence ; Amino acids ; Causes of ; Child, Preschool ; Exome - genetics ; Female ; Gene mutations ; Genetic disorders ; Genetic research ; Hand Deformities, Congenital - enzymology ; Hand Deformities, Congenital - genetics ; Haplotypes ; Heterozygote ; Homozygote ; Humans ; Infant ; Male ; Metabolism ; Middle Aged ; Models, Molecular ; Molecular Sequence Data ; Mutation ; Oxidoreductases - genetics ; Oxidoreductases - metabolism ; Pedigree ; Pierre Robin Syndrome - enzymology ; Pierre Robin Syndrome - genetics ; Report ; Research ; Sequence Alignment ; Sequence Analysis, DNA ; Young Adult
ISSN:
0002-9297
E-ISSN:
1537-6605
DOI:
10.1016/j.ajhg.2014.11.004
Source:
PubMed Central
URL:
https://www.ncbi.nlm.nih.gov/pubmed/25480037$$D View this record in MEDLINE/PubMed
