Homozygous and compound-heterozygous mutations in TGDS cause Catel-Manzke syndrome.
نویسندگان
چکیده
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.
منابع مشابه
Catel–Manzke syndrome: Further delineation of the phenotype associated with pathogenic variants in TGDS
Catel-Manzke syndrome is a rare autosomal recessive disorder characterized by Pierre Robin sequence with hyperphalangy and clinodactyly of the index finger. Recently, homozygous or compound heterozygous pathogenic variants in TGDS have been discovered to cause Catel-Manzke syndrome. Here, we describe a 12-month-old male with molecularly confirmed Catel-Manzke syndrome who presented with Pierre ...
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ورودعنوان ژورنال:
- American journal of human genetics
دوره 95 6 شماره
صفحات -
تاریخ انتشار 2014