Array comparative genomic hybridisation-based identification of two imbalances of chromosome 1p in a 9-year-old girl with a monosomy 1p36 related phenotype and a family history of learning difficulties: a case report

Abstract

Introduction: Monosomy 1p36 is one of the most common terminal deletion syndromes, with an approximate incidence of 1 in every 5000 live births. This syndrome is associated with several pronounced clinical features including characteristic facial features, cardiac abnormalities, seizures and mental retardation, all of which are believed to be due to haploinsufficiency of genes within the 1p36 region. The deletion size varies from approximately 1.5 Mb to 10 Mb with the most common breakpoints located at 1p36.13 to 1p36.33. Over 70% of 1p36 deletion patients have a true terminal deletion. A further 7% have interstitial deletions and a proportion have a derivative chromosome 1 where the 1p telomere is replaced by material from another chromosome, either as a result of a de-novo rearrangement or as a consequence of malsegregation of a balanced parental translocation at meiosis.

Role of Phosphoinositide-Specific Phospholipase C η2 in Isolated and Syndromic Mental Retardation

“…In fact, molecular cytogenetic analysis performed in 1 patient presenting with MR and learning disability detected the presence of GABRD loci. These data suggested to exclude the involvement of GABRD in the neurological manifestations [36]. Moreover, the 1p36.32 region was found deleted in a small percentage of isolated MR [16], in a number of patients presenting with mild MR and/or behavioral problems and/or learning disability [12,24,25,26,27,28] and in a patient presenting with MR and altered regulation of the circadian rhythm such as sleeping disorders [26].…”

“…By contrast, the finding of a patient bearing a complex rearrangement including 1p36.32 deletion in which GABRD locus was not involved suggested that the neurological features might be correlated to the anomalous expression of other genes [36]. The patient, a 9-year-old female, presented with dysmorphic features including a small mouth with heaped-up palate, small chin and small overfolded ears, straight eyebrows, fifth finger clinodactyly and short toes.…”

“…Developmental retardation such as delayed ability to sit, speech delay, and late walking at 22 months was also reported. Molecular cytogenetic analyses in the proband detected 1p36.32 deletion between 1.4 and 2 Mb long not involving the GABRD locus [36]. The authors suggested the existence of association among learning difficulties, developmental delay and 1p36.32 deletion.…”

“…The authors suggested the existence of association among learning difficulties, developmental delay and 1p36.32 deletion. Further analyses detected deletion of the phosphoinositide (PI)-specific phospholipase C (PI-PLC) η2 codifying gene (PLCH2; OMIM *612836), which maps on 1p36.32 [36] (fig. 1).…”

Pesquisa dos mecanismos de rearranjos cromossômicos subteloméricos na monossomia 1p36, expansão do espectro da variabilidade fenotípica e comportamental, diagnósticos diferenciais e caracterização de uma região crítica para obesidade

“…Apart two previously known candidate genes (SKI and PEX10), we drawn attention to three genes mapped to this region: PRKCZ, PLCH2, and HES5. Recently, Fitzgibbon et al (2008), based on the expression of PLCH2 gene in cerebral cortex, speculated on a possible association between PLCH2 deletion and learning difficulties, developmental delay and speech delay in a patient with complex rearrangement of 1p36.…”