Breakpoint delineation in 5p‐ patients leads to new insights about microcephaly and the typical high‐pitched cry

Chehimi, Samar N.; Zanardo, Évelin Aline; Ceroni, Jose R. M.; Nascimento, A. M.; Madia, F. A. R.; Dias, Alexandre Torchio; Filho, Gil Monteiro Novo; Montenegro, Marília M.; Damasceno, Jullian Gabriel; Costa, Thaís Virgínia Moura Machado; Gasparini, Yanca; Kim, Chong; Kulikowski, Leslie Domenici

doi:10.1002/mgg3.957

Cited by 5 publications

(6 citation statements)

References 32 publications

(36 reference statements)

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“…The phenotypic variability of CdCS has been associated with the heterogeneity of the deletion size, position, and gene content at the short arm of chromosome 5. The deletions vary in size, but breakpoints have been mainly described within bands 5p15.2 or 5p15.3 [Chehimi et al, 2020].…”

Section: Discussionmentioning

confidence: 99%

Cri-du-Chat Syndrome: Revealing a Familial Atypical Deletion in 5p

et al. 2022

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Introduction: Cri-du-chat syndrome is generally diagnosed when patients present a high-pitched cry at birth, microcephaly, ocular hypertelorism, and prominent nasal bridge. The karyotype is useful to confirm deletions in the short arm of chromosome 5 (5p–) greater than 10 Mb. In cases of smaller deletions, it is necessary to resort to other molecular techniques such as fluorescence in situ hybridization, multiplex ligation-dependent probe amplification (MLPA) or genomic array. Case Presentation: We report a family with an atypical deletion in 5p (mother and 2 children) and variable phenotypes compared with the literature. We applied a P064 MLPA kit to evaluate 5p– in the mother and the 2 children, and we used the Infinium CytoSNP-850K BeadChip genomic array to evaluate the siblings, an 11-year-old boy and a 13-year-old girl, to better define the 5p breakpoints. Both children presented a high-pitched cry at birth, but they did not present any of the typical physical features of 5p– syndrome. The MLPA technique with 5 probes for the 5p region revealed that the patients and their mother presented an atypical deletion with only 4 probes deleted (TERT_ex2, TERT_ex13, CLPTM1L, and IRX4). The genomic array performed in the siblings’ samples revealed a 6.2-Mb terminal deletion in 5p15.33p15.32, which was likely inherited from their mother, who presented similar molecular features, seen in MLPA. Discussion: The sparing of the CTNND2 gene, which is associated with cerebral development, in both siblings may explain why these 2 patients had features such as better communication skills which most patients with larger 5p deletions usually do not present. In addition, both patients had smaller deletions than those found in patients with a typical 5p– phenotype. This report demonstrates the utility of genomic arrays as a diagnostic tool to better characterize atypical deletions in known syndromes such as 5p– syndrome, which will allow a better understanding of the genotype-phenotype correlations.

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Section: Discussionmentioning

confidence: 99%

Cri-du-Chat Syndrome: Revealing a Familial Atypical Deletion in 5p

et al. 2022

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“…During the A.B.C family meetings held from 2014 to 2018, we evaluated the voice of 63 consecutive Italian CdC patients; for all of them, the diagnosis of Cri du Chat syndrome was obtained by karyotype studies, showing a terminal deletion of the short arm of chromosome [5]. As array CGH is available only in a minority of cases, the ones with the most recent diagnoses, we did not attempt a correlation between clinical and molecular data.…”

Section: Methodsmentioning

confidence: 99%

“…Cortical regions work with the basal ganglia, thalamus and cerebellum in speech control [4]. A recent paper [5] identified a small region, 5p15.2, included in the 5p-deletions as related to a high-pitched voice in CdC patients, although the data are not fully conclusive.…”

Section: Introductionmentioning

confidence: 99%

Voice Analysis in 63 Italian Cri du Chat Patients

2023

J Family Med Prim Care Open Acc

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Objectives:The aim of our work was to identify, specific abnormalities in vocal pattern, eventually actionable to logotherapy, in patients with Cri du Chat Syndrome (CdC) who present a peculiar, abnormal cry in newborns, possibly explained by anatomical or neurological alterations. Study Design: It is a descriptive study with a prospective collection of voice profile data. Methods: We recorded the data relative to fundamental frequency (Fo), stiff vocal attachment, intelligibility by the listener, and diplophonia. Spectrographic analysis was performed using a Computer Speech Lab recording system and the speech analysis package XYZ. Results: We report on voice analysis in a group of 63 Italian CdC patients: 28 infants and children (15 males) and 35 adults (20 males). No differences were observed between sexes in the mean age of onset of linguistic production, which was 2 years 4 months for males and 2 years 11 months for females. The mean and SD of Fo in infant and children CdC showed that 5/13 females, and 6/15 males were below normal limits. All adult CdC females, but one, showed Fo within normal limits; Fo is increased above the normal range in all but one adult CdC male. The percentage of stiff vocal attachment increases with age, as it is present in 30/40% of F/M infants and 66/65% of F/M adults. Intelligibility by the listener improves with age in both sexes. Forced voice was present in 46.6% of infants and 65% of adult males and 30.7% and 66.6% in infant and adult females, respectively. Diplophonia was present only in adults, in 15% and 20% of males and females, respectively. Conclusion: Any improvement in verbal communication, even within a picture of developmental delay, may result in favorable improvement of social relationship. We comment also on the relevance of a personalized logopedic therapy, to be started as early as possible in childhood, and to be continued also in older ages.

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“…Genomic data were collected from the literature where approximate breakpoints are known for 53 individuals with 9p deletion and duplication syndromes. 12 , 14 , 15 , 16 , 17 , 19 , 27 , 29 , 30 , 33 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 …”

Section: Methodsmentioning

confidence: 99%

From karyotypes to precision genomics in 9p deletion and duplication syndromes

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Tate

et al. 2022

Human Genetics and Genomics Advances

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While 9p deletion and duplication syndromes have been studied for several years, small sample sizes and minimal high-resolution data have limited a comprehensive delineation of genotypic and phenotypic characteristics. In this study, we examined genetic data from 719 individuals in the worldwide 9p Network Cohort: a cohort seven to nine times larger than any previous study of 9p. Most breakpoints occur in bands 9p22 and 9p24, accounting for 35% and 38% of all breakpoints, respectively. Bands 9p11 and 9p12 have the fewest breakpoints, with each accounting for 0.6% of all breakpoints. The most common phenotype in 9p deletion and duplication syndromes is developmental delay, and we identified eight known neurodevelopmental disorder genes in 9p22 and 9p24. Since it has been previously reported that some individuals have a secondary structural variant related to the 9p variant, we examined our cohort for these variants and found 97 events. The top secondary variant involved 9q in 14 individuals (1.9%), including ring chromosomes and inversions. We identified a gender bias with significant enrichment for females (p = 0.0006) that may arise from a sex reversal in some individuals with 9p deletions. Genes on 9p were characterized regarding function, constraint metrics, and protein-protein interactions, resulting in a prioritized set of genes for further study. Finally, we achieved precision genomics in one child with a complex 9p structural variation using modern genomic technologies, demonstrating that long-read sequencing will be integral for some cases. Our study is the largest ever on 9p-related syndromes and provides key insights into genetic factors involved in these syndromes.

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Breakpoint delineation in 5p‐ patients leads to new insights about microcephaly and the typical high‐pitched cry

Cited by 5 publications

References 32 publications

Cri-du-Chat Syndrome: Revealing a Familial Atypical Deletion in 5p

Cri-du-Chat Syndrome: Revealing a Familial Atypical Deletion in 5p

Voice Analysis in 63 Italian Cri du Chat Patients

From karyotypes to precision genomics in 9p deletion and duplication syndromes

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