Cryptic 7q21 and 9p23 deletions in a patient with apparently balanced de novo reciprocal translocation t(7;9)(q21;p23) associated with a dystonia-plus syndrome: paternal deletion of the epsilon-sarcoglycan (SGCE) gene

Abstract

We report on a boy with myoclonus-dystonia (M-D), language delay, and malformative anomalies. Genetic investigations allowed the identification of an apparently balanced de novo reciprocal translocation, t(7;9)(q21;p23). Breakpoint-region mapping using fluorescent in situ hybridization (FISH) analysis of bacterial artificial chromosome (BAC) clone probes identified microdeletions of 3.7 and 5.2 Mb within 7q21 and 9p23 breakpoint regions, respectively. Genotyping with microsatellite markers showed that deletions originated from paternal alleles. The deleted region on chromosome 7q21 includes a large imprinted gene cluster. SGCE and PEG10 are two maternally imprinted genes. SGCE mutations are implicated in M-D. In our case, M-D is due to deletion of the paternal allele of the SGCE gene. PEG10 is strongly expressed in the placenta and is essential for embryo development. Prenatal growth retardation identified in the patient may be due to deletion of the paternal allele of the PEG10 gene. Other genes in the deleted region on chromosome 7 are not imprinted. Nevertheless, a phenotype can be due to haploinsufficiency of these genes. KRIT1 is implicated in familial forms of cerebral cavernous malformations, and COL1A2 may be implicated in very mild forms of osteogenesis imperfecta. The deleted region on chromosome 9 overlaps with the candidate region for monosomy 9p syndrome. The proband shows dysmorphic features compatible with monosomy 9p syndrome, without mental impairment. These results emphasize that the phenotypic abnormalities of apparently balanced de novo translocations can be due to cryptic deletions and that the precise mapping of these aneusomies may improve clinical management.

Deleterious Effects of Beta-Blockers on Survival in Patients With Cirrhosis and Refractory Ascites†,‡

“…Several nonsense and small‐deletion mutations have been reported independently and thus appear to be recurrent mutations 179. In addition, exonic deletion mutations180, 181 and other larger deletions have also been reported 182–184. These latter deletions do correlate with phenotype, as they also remove other nearby genes and result in more complex manifestations including skeletal abnormalities, facial dysmorphism, developmental delay, or cavernous cerebral malformations 182–184.…”

“…In addition, exonic deletion mutations180, 181 and other larger deletions have also been reported 182–184. These latter deletions do correlate with phenotype, as they also remove other nearby genes and result in more complex manifestations including skeletal abnormalities, facial dysmorphism, developmental delay, or cavernous cerebral malformations 182–184. Finally, maternal uniparental disomy can also cause M‐D because of imprinting (inactivation) of both maternal genes 185…”

Myoclonus‐dystonia: An update

“…In this setting, disorders associated with M‐D depend on the deletion breakpoints. They may include intrauterine growth retardation and short stature, microcephaly and facial dysmorphism, developmental delay, cerebral cavernous malformation, hearing loss, and skeletal or joint disorders 10, 15, 62, 71. Finally, M‐D syndrome due to SGCE deficiency can result from maternal uniparental disomy of chromosome 7 owing to methylation, thus silencing the two maternal alleles 72.…”

Investigation of the candidate region for trigonocephaly in a patient with monosomy 9p syndrome using array‐CGH

“…4). Bonnet et al 2008 reported a patient with balanced translocation t(7;9)(q21;p23), which derived a cryptic deletion on each breakpoint. Since the deletion region did not overlap with the critical region reported by Swinkels et al 2008, it would be reasonable to suggest that the patient did not show trigonocephaly (Fig.…”