title: Whole gene duplication of the PQBP1 gene in syndrome resembling Renpenning.
abstract: Renpenning syndrome is a well-described X-linked condition associated with multiple congenital anomalies and intellectual disability [OMIM 309500]. Typical signs include microcephaly, dysmorphic features, short stature, small testes, and lean body build. Renpenning syndrome is caused by mutations in the polyglutamine binding protein 1 (PQBP1) gene. Missense mutations, insertions, deletions, and duplications within the gene have been well-described. We present a 47-year-old male with clinical features resembling Renpenning syndrome. He has moderate intellectual disability, seizures since infancy, short stature, small testes, and dysmorphic features. Of note, our patient is normocephalic. A CT scan at 14 years of age showed cerebral atrophy. He had previously been verbally communicative and had few behavioral issues. Recently, our patient has regressed and has become uncommunicative, displaying little and unclear speech. He now exhibits memory and recognition loss and is uncooperative, aggressive, self-abusive, and incontinent. The reason for his regression within the past 4 years is unclear. SNP microarray analysis (500K) revealed a 4.7 Mb duplication at Xp11.22-p11.23. Multiple ligation probe amplification (MLPA) of the PQBP1 gene contained within this duplicated region confirmed a duplication of the entire PQBP1 gene. Multiple other genes are duplicated within this 4.7 Mb region and may contribute to his phenotype.
authors.affiliation: Center for Human Genetics, Boston University School of Medicine, Massachusetts 02118, USA.
authors.forename: Maureen
authors.initials: M
authors.lastname: Flynn
authors.forename: Ying S
authors.initials: YS
authors.lastname: Zou
authors.forename: Aubrey
authors.initials: A
authors.lastname: Milunsky
mesh_terms: D002352:Carrier Proteins / Q000235:genetics*; D002547:Cerebral Palsy / Q000235:genetics; D002869:Chromosome Aberrations; D041321:Chromosomes, Human, X / Q000235:genetics*; D004268:DNA-Binding Proteins; D018450:Disease Progression; D020440:Gene Duplication / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D038901:X-Linked Intellectual Disability / Q000235:genetics; D046228:Microarray Analysis; D009687:Nuclear Proteins / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics
chemical_list: D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C119246:PQBP1 protein, human