Blepharophimosis and mental retardation (BMR) phenotypes caused by chromosomal rearrangements: Description in a boy with partial trisomy 10q and monosomy 4q and review of the literature

Bartholdi, Deborah; Toelle, Sandra P.; Steiner, Bernhard; Boltshauser, Eugen; Schinzel, Albert; Riegel, Mariluce

doi:10.1016/j.ejmg.2007.12.005

Cited by 18 publications

(26 citation statements)

References 26 publications

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“…A third comparable case (DECIPHER patient 264658) overlapped our patient's gain by approximately 15 Mb and presented with facial abnormality, blepharophimosis, and ptosis, which are phenotypes that are consistent with the milder clinical features seen in more distal duplications [Carter et al, 2010]. Several other comparable duplications are mostly derived from a translocation and have been described as distal 10q trisomy syndrome [e.g., Bartholdi et al, 2008;Al-Sarraj et al, 2014]. Common and not so common features found in this syndrome and present in our patient include DD/ID, growth retardation, blepharophimosis, flat face, flat nasal bridge, Hemming et al [2016].…”

Section: Discussionmentioning

confidence: 80%

Familial 3-Way Balanced Translocation Causes 1q43→qter Loss and 10q25.2→qter Gain in a Severely Affected Male Toddler

Córdova-Fletes

Arámbula-Meraz

Zarazúa-Niño

et al. 2019

Cytogenet Genome Res

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Constitutional complex chromosomal rearrangements (CCRs) are rare events that typically involve 2 or more chromosomes with at least 3 breakpoints and can result in normal or abnormal phenotypes depending on whether they disturb the euchromatic neighborhood. Here, we report an unusual balanced CCR involving chromosomes 1, 9, and 10 that causes an unbalanced karyotype in a severely affected toddler. The CCR was initially reported as a maternal 2-way translocation but was reclassified as a 3-way translocation after a microarray analysis of the propositus revealed the involvement of another chromosome not identified by G-banding in his phenotypically normal mother. FISH assays on maternal metaphase cells confirmed that the 1qter region of der(1) was translocated to der(10), whereas the 10qter segment was translocated to der(9), which in turn donated a segment to der(1). Subsequently, this CCR was also identified in her phenotypically normal father (the patient's grandfather). Thus, the patient inherited the previously unreported pathogenic combination of der(1) with a loss of 1q43→qter (including AKT3, ZBTB18, HNRNPU, and SMYD3) and der(9) with a gain of 10q25.2→qter (including FGFR2), leading to a compound phenotype with key features of the 1q43→qter deletion and distal 10q trisomy syndromes. Our observations suggest that the loss of SMYD3 accounts for cardiac defects in a subset of patients. Moreover, due to recurrent miscarriages in this family, our findings allowed improved genetic counseling.

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Section: Discussionmentioning

confidence: 80%

Familial 3-Way Balanced Translocation Causes 1q43→qter Loss and 10q25.2→qter Gain in a Severely Affected Male Toddler

Córdova-Fletes

Arámbula-Meraz

Zarazúa-Niño

et al. 2019

Cytogenet Genome Res

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“…This patient displayed the following clinical features: blepharophimosis, ptosis, epicanthus inversus, downslanting palpebral Wssures, generalized hypotonia and developmental delay. The phenotype was ascribed to the duplication of chromosome 10q (Bartholdi et al 2008). Our patient 7 showed a similar phenotype; therefore, we hypothesize that the duplication of chromosome 10q might contribute to the BPES-like phenotype in this patient.…”

Section: Complex Cnvsmentioning

confidence: 75%

“…Patient 7 was found to carry a terminal duplication of chromosome 10q (21.9 Mb) and a terminal deletion of chromosome 11q (5 Mb). Recently, a patient was described with approximately the same duplication of chromosome 10q and a deletion located on chromosome 4q (Bartholdi et al 2008). This patient displayed the following clinical features: blepharophimosis, ptosis, epicanthus inversus, downslanting palpebral Wssures, generalized hypotonia and developmental delay.…”

Section: Complex Cnvsmentioning

confidence: 99%

“…From 135 syndromes in the London Dysmorphology Database with blepharophimosis and ptosis, six are known to be associated with a chromosomal microdeletion (Winter and Baraitser 2008). In addition, a recent literature review illustrates that chromosomal aberrations are probably the most important underlying cause in patients with blepharophimosis and mental retardation phenotypes (Bartholdi et al 2008). Only a few blepharophimosis syndromes have known causative genes: the Schwartz-Jampel syndrome (OMIM 255800), Freeman Sheldon syndrome (OMIM 193700), Hereditary neuralgic amyotrophy syndrome (HNA; OMIM 162100) (Laccone et al 2008) and Blepharophimosis-Ptosis-Epicanthus inversus syndrome (BPES) (OMIM 110100).…”

Section: Introductionmentioning

confidence: 99%

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Identification of copy number variants associated with BPES-like phenotypes

et al. 2008

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Blepharophimosis-Ptosis-Epicanthus inversus syndrome (BPES) is a well-characterized rare syndrome that includes an eyelid malformation associated with (type I) or without premature ovarian failure (type II). Patients with typical BPES have four major characteristics: blepharophimosis, ptosis, epicanthus inversus and telecanthus. Mutations in the FOXL2 gene, encoding a forkhead transcription factor, are responsible for the majority of both types of BPES. However, many patients with BPES-like features, i.e., having at least two major characteristics of BPES, have an unidentiWed cause. Here, we report on a group of 27 patients with BPES-like features, but without an identiWed genetic defect in the FOXL2 gene or Xanking region. These patients were analyzed with whole-genome high-density arrays in order to identify copy number variants (CNVs) that might explain the BPES-like phenotype. In nine out of 27 patients (33%) CNVs not previously described as polymorphisms were detected. Four of these patients displayed psychomotor retardation as an additional clinical characteristic. In conclusion, we demonstrate that BPES-like phenotypes are frequently caused by CNVs, and we emphasize the importance of whole-genome copy number screening to identify the underlying genetic causes of these phenotypes.

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“…Only a few patients belong to the pure distal 10q duplication category. Some previous studies showed that even different partner chromosomes are involved, that the phenotypes of patients can mainly be ascribed to the 10q duplication and that the concomitant monosomy likely does not influence the clinical features substantially [Briscioli et al, 1993;Bartholdi et al, 2008]. We only included 4 patients with molecularly defined pure distal 10q duplication together with 2 patients with inv dup del 10q and our patient in a phenotype comparision ( table 1 ) [Devriendt et al, 1999;Petek et al, 2001;Migliori et al, 2002;Hou, 2003;Carter et al, 2010;Sarri et al, 2011].…”

Section: Discussionmentioning

confidence: 99%

Inverted Duplication and Deletion of 10q25q26 in a Patient without Any Obvious Skeletal Anomalies

Xiao

Xing

et al. 2012

Mol Syndromol

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We report on a girl with inverted duplication and deletion of 10q25q26 revealed by array-CGH and FISH analysis. Array-CGH analysis demonstrated a ∼13.1-Mb duplication encompassing 10q25.3q26.2 and a ∼5-Mb deletion at 10q26.2q26.3. No single-copy region was detected between the deleted and duplicated segments. FISH analysis found the arrangement duplicated in an inverted position. FISH analysis using the same probes did not show any abnormality in both parents, which indicates a de novo occurrence. The frequently reported features of distal 10q duplication include developmental delay, blepharophimosis, hypotonia, skeletal anomalies and some facial dysmorphisms. The girl presented with many features of distal 10q duplication with the exception of skeletal anomalies. To our knowledge, this is the fourth patient reported in the literature with inv dup del 10q. 10q duplication seems to account for most of the phenotypes for our patient. Although no obvious skeletal feature was found in our patient at present, follow-up assessment of skeletal development should be planned with the increase of age.

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Blepharophimosis and mental retardation (BMR) phenotypes caused by chromosomal rearrangements: Description in a boy with partial trisomy 10q and monosomy 4q and review of the literature

Cited by 18 publications

References 26 publications

Familial 3-Way Balanced Translocation Causes 1q43→qter Loss and 10q25.2→qter Gain in a Severely Affected Male Toddler

Familial 3-Way Balanced Translocation Causes 1q43→qter Loss and 10q25.2→qter Gain in a Severely Affected Male Toddler

Identification of copy number variants associated with BPES-like phenotypes

Inverted Duplication and Deletion of 10q25q26 in a Patient without Any Obvious Skeletal Anomalies

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Blepharophimosis and mental retardation (BMR) phenotypes caused by chromosomal rearrangements: Description in a boy with partial trisomy 10q and monosomy 4q and review of the literature

Cited by 18 publications

References 26 publications

Familial 3-Way Balanced Translocation Causes 1q43&#x2192;qter Loss and 10q25.2&#x2192;qter Gain in a Severely Affected Male Toddler

Familial 3-Way Balanced Translocation Causes 1q43&#x2192;qter Loss and 10q25.2&#x2192;qter Gain in a Severely Affected Male Toddler

Identification of copy number variants associated with BPES-like phenotypes

Inverted Duplication and Deletion of 10q25q26 in a Patient without Any Obvious Skeletal Anomalies

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Familial 3-Way Balanced Translocation Causes 1q43→qter Loss and 10q25.2→qter Gain in a Severely Affected Male Toddler

Familial 3-Way Balanced Translocation Causes 1q43→qter Loss and 10q25.2→qter Gain in a Severely Affected Male Toddler