A novel Xp22.11 deletion causing a syndrome of craniosynostosis and periventricular nodular heterotopia

Kogelenberg, Margriet van; Lerone, Margherita; Toni, Teresa De; Divizia, Maria Teresa; Brouwer, Arjan P.M. de; Veltman, Joris A.; Bokhoven, Hans van; Robertson, Stephen P.

doi:10.1002/ajmg.a.34311

Cited by 5 publications

(1 citation statement)

References 20 publications

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“…Mutations in X-linked filamin A (FLNA) [Lange et al, 2015] and ADP-ribosylation factor guanine nucleotide-exchange factor 2 (ARFGEF2) [Bardón-Cancho et al, 2014] are the most common causes of gray matter heterotopias. In addition, other rare causes have also been reported, such as deletions of 1p36 [Neal et al, 2006], 11q24 [So et al, 2014], or Xp22.11 [van Kogelenberg et al, 2011] or mutations in the C6orf70 gene [Conti et al, 2013], which have also gotten much attention in our study. C6orf70 (chromosome 6 open reading frame 70) is ubiquitously highly expressed in the brain and is dosage sensitive.…”

Section: Discussionmentioning

confidence: 80%

Gray Matter Heterotopia, Mental Retardation, Developmental Delay, Microcephaly, and Facial Dysmorphisms in a Boy with Ring Chromosome 6: A 10-Year Follow-Up and Literature Review

Liu

Wang

Wei

et al. 2018

Cytogenet Genome Res

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Ring chromosome 6, r(6), is an extremely rare cytogenetic abnormality with clinical heterogeneity which arises typically de novo. The phenotypes of r(6) can be highly variable, ranging from almost normal to severe malformations and neurological defects. Up to now, only 33 cases have been reported in the literature. In this 10-year follow-up study, we report a case presenting distinctive facial features, severe developmental delay, and gray matter heterotopia with r(6) and terminal deletions of 6p25.3 (115426-384174, 268 kb) and 6q26-27 (168697778-170732033, 2.03 Mb) encompassing 2 and 15 candidate genes, respectively, which were detected using G-banding karyotyping, FISH, and chromosomal microarray analysis. We also analyzed the available information on the clinical features of the reported r(6) cases in order to provide more valuable information on genotype-phenotype correlations. To the best of our knowledge, this is the first report of gray matter heterotopia manifested in a patient with r(6) in China, and the deletions of 6p and 6q in our case are the smallest with the precise size of euchromatic material loss currently known.

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Section: Discussionmentioning

confidence: 80%

Gray Matter Heterotopia, Mental Retardation, Developmental Delay, Microcephaly, and Facial Dysmorphisms in a Boy with Ring Chromosome 6: A 10-Year Follow-Up and Literature Review

Liu

Wang

Wei

et al. 2018

Cytogenet Genome Res

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Periventricular nodular heterotopia in Smith‐Magenis syndrome

Capra

Biancheri

Morana

et al. 2014

American J of Med Genetics Pt A

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Smith-Magenis syndrome (SMS) is caused by an interstitial microdeletion of chromosome 17p11.2. A few patients with the typical SMS phenotype have RAI1 gene mutations. The syndrome is characterized by minor craniofacial anomalies, short stature, sleep disturbances, behavioural and neurocognitive abnormalities, as well as variable multisystemic manifestations. Periventricular nodular heterotopia (PNH) is a genetically heterogeneous neuronal migration disorder characterized by subependymal heterotopic nodules, and is variably associated with other brain malformations, epileptic seizures and intellectual disability. Here we report on two patients harboring deletions of the 17p11.2 region in whom the SMS typical phenotype was associated with bilateral PNH. Our observations expand the spectrum of chromosomal rearrangements associated with PNH and indicate that abnormal neuronal migration may contribute to the neurocognitive phenotype of SMS.

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Functional monosomy of 6q27‐qter and functional disomy of Xpter‐p22.11 due to X;6 translocation with an atypical X‐inactivation pattern

Podolska

Kobelt

Fuchs

et al. 2017

American J of Med Genetics Pt A

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Pattern of X chromosome inactivation (XCI) is typically random in females. However, chromosomal rearrangements affecting the X chromosome can result in XCI skewing due to cell growth disadvantage. In case of an X;autosome translocation, this usually leads to an XCI pattern of 100:0 with the derivative X being the active one in the majority of females. A de novo balanced X;6 translocation [46,X,t(X;6)(p22.1;q27)] and a completely skewed XCI pattern (100:0) were detected in a female patient with microcephaly, cerebellar vermis hypoplasia, heart defect, and severe developmental delay. We mapped the breakpoint regions using fluorescence in situ hybridization and found the X-linked gene POLA1 to be disrupted. POLA1 codes for the catalytic subunit of the polymerase α-primase complex which is responsible for initiation of the DNA replication process; absence of POLA1 is probably incompatible with life. Consequently, by RBA banding we determined which of the X chromosomes was the active one in the patient. In all examined lymphocytes the wild-type X chromosome was active. We propose that completely skewed XCI favoring the normal X chromosome resulted from death of cells with an active derivative X that was caused by a non-functional POLA1 gene. In summary, we conclude that functional monosomy of 6q27-qter and functional disomy of Xpter-p22.11 are responsible for the clinical phenotype of the patient. This case demonstrates the importance of determining which one of the X chromosomes underwent inactivation to correlate clinical features of a female with an X;autosome translocation with the nature of the genetic alteration.

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A novel Xp22.11 deletion causing a syndrome of craniosynostosis and periventricular nodular heterotopia

Cited by 5 publications

References 20 publications

Gray Matter Heterotopia, Mental Retardation, Developmental Delay, Microcephaly, and Facial Dysmorphisms in a Boy with Ring Chromosome 6: A 10-Year Follow-Up and Literature Review

Gray Matter Heterotopia, Mental Retardation, Developmental Delay, Microcephaly, and Facial Dysmorphisms in a Boy with Ring Chromosome 6: A 10-Year Follow-Up and Literature Review

Periventricular nodular heterotopia in Smith‐Magenis syndrome

Functional monosomy of 6q27‐qter and functional disomy of Xpter‐p22.11 due to X;6 translocation with an atypical X‐inactivation pattern

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