TRAPPC9-related autosomal recessive intellectual disability: report of a new mutation and clinical phenotype

Giuseppe Marangi, Marcella Zollino, Serena Lattante, Daniela Orteschi, Giovanni Neri, Vincenzo Leuzzi, Filippo Manti, Vanna Pecile

Risultato della ricerca: Contributo in rivistaArticolo in rivistapeer review

41 Citazioni (Scopus)

Abstract

Intellectual disability (ID) with autosomal recessive (AR) inheritance is believed to be common; however, very little is known about causative genes and genotype-phenotype correlations. The broad genetic heterogeneity of AR-ID, and its usually nonsyndromic nature make it difficult to pool multiple pedigrees with the same underlying genetic defect to achieve consistent nosology. Nearly all autosomal genes responsible for recessive cognitive disorders have been identified in large consanguineous families from the Middle East, and nonsense mutations in TRAPPC9 have been reported in a total of 5. Although several recurrent phenotypic abnormalities are described in some of these patients, the associated phenotype is usually referred to as nonsyndromic. By means of single-nucleotide polymorphism-array first and then by exome sequencing, we identified a new pathogenic mutation in TRAPPC9 in two Italian sisters born to healthy and apparently nonconsanguineous parents. It consists of a homozygous splice site mutation causing exon skipping with frameshift and premature termination, as confirmed by mRNA sequencing. By detailed phenotypic analysis of our patients, and by critical literature review, we found that homozygous TRAPPC9 loss-of-function mutations cause a distinctive phenotype, characterized by peculiar facial appearance, obesity, hypotonia (all signs resembling a Prader-Willi-like phenotype), moderate-to-severe ID, and consistent brain abnormalities.European Journal of Human Genetics advance online publication, 2 May 2012; doi:10.1038/ejhg.2012.79.
Lingua originaleEnglish
pagine (da-a)229-232
Numero di pagine4
RivistaEuropean Journal of Human Genetics
Volume2013
DOI
Stato di pubblicazionePubblicato - 2013

Keywords

  • TRAPPC9
  • autosomal recessive intellectual disability
  • exome sequencing

Fingerprint

Entra nei temi di ricerca di 'TRAPPC9-related autosomal recessive intellectual disability: report of a new mutation and clinical phenotype'. Insieme formano una fingerprint unica.

Cita questo