Dataset Information

Cytogenomic delineation and clinical follow-up of two siblings with an 8.5 Mb 6q24.2-q25.2 deletion inherited from a paternal insertion.

ABSTRACT: The chromosomal segment 6q24-q25 comprises a contiguous gene microdeletion syndrome characterized by intrauterine growth retardation, growth delay, intellectual disability, cardiac anomalies, and a dysmorphic facial phenotype. We describe here a 10-year follow-up with detailed clinical, neuropsychological, and cytomolecular data of two siblings, male and female, who presented with developmental delay, microcephaly, short stature, characteristic facial dysmorphisms, multiple organ anomalies, and intellectual disability. Microarray analysis showed an 8.5 Mb 6q24.2-q25.2 interstitial deletion. Fluorescence in situ hybridization analyses confirmed the deletions and identified an insertion of 6q into 8q13 in their father, resulting in a high recurrence risk. This is the first report in sibs with distinct neuropsychological involvement, one of them with stenosis of the descending branch of the aorta.

SUBMITTER: Meloni VA

PROVIDER: S-EPMC4882109 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature

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Cytogenomic delineation and clinical follow-up of two siblings with an 8.5 Mb 6q24.2-q25.2 deletion inherited from a paternal insertion.

Meloni Vera Ayres VA Guilherme Roberta Santos RS Oliveira Mariana Moyses MM Migliavacca Michele M Takeno Sylvia Satomi SS Sobreira Nara Lygia Macena NL de Fatima Faria Soares Maria M de Mello Claudia Berlim CB Melaragno Maria Isabel MI

American journal of medical genetics. Part A 20140604 9

The chromosomal segment 6q24-q25 comprises a contiguous gene microdeletion syndrome characterized by intrauterine growth retardation, growth delay, intellectual disability, cardiac anomalies, and a dysmorphic facial phenotype. We describe here a 10-year follow-up with detailed clinical, neuropsychological, and cytomolecular data of two siblings, male and female, who presented with developmental delay, microcephaly, short stature, characteristic facial dysmorphisms, multiple organ anomalies, and ...[more]

PMID: 24898331

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Project description:PURPOSE:Inherited peripheral neuropathies (IPN) represent a large heterogenous group of hereditary diseases with more than 100 causative genes reported to date. In this context, targeted next-generation sequencing (NGS) offers the opportunity to screen all these genes with high efficiency in order to unravel the genetic basis of the disease. Here, we compare the diagnostic yield of targeted NGS with our previous gene by gene Sanger sequencing strategy. We also describe several novel likely pathogenic variants. DESIGN AND PARTICIPANTS:We have completed the targeted NGS of 81 IPN genes in a cohort of 123 unrelated patients affected with diverse forms of IPNs, mostly Charcot-Marie-Tooth disease (CMT): 23% CMT1, 52% CMT2, 9% distal hereditary motor neuropathy, 7% hereditary sensory and autonomic neuropathy and 6.5% intermediate CMT. RESULTS:We have solved the molecular diagnosis in 49 of 123 patients (~40%). Among the identified variants, 26 variants were already reported in the literature. In our cohort, the most frequently mutated genes are respectively: MFN2, SH3TC2, GDAP1, NEFL, GAN, KIF5A and AARS. Panel-based NGS was more efficient in familial cases than in sporadic cases (diagnostic yield 49%vs19%, respectively). NGS-based search for copy number variations, allowed the identification of three duplications in three patients and raised the diagnostic yield to 41%. This yield is two times higher than the one obtained previously by gene Sanger sequencing screening. The impact of panel-based NGS screening is particularly important for demyelinating CMT (CMT1) subtypes, for which the success rate reached 87% (36% only for axonal CMT2). CONCLUSION:NGS allowed to identify causal mutations in a shorter and cost-effective time. Actually, targeted NGS is a well-suited strategy for efficient molecular diagnosis of IPNs. However, NGS leads to the identification of numerous variants of unknown significance, which interpretation requires interdisciplinary collaborations between molecular geneticists, clinicians and (neuro)pathologists.

Dataset Information

Cytogenomic delineation and clinical follow-up of two siblings with an 8.5 Mb 6q24.2-q25.2 deletion inherited from a paternal insertion.

Publications

Cytogenomic delineation and clinical follow-up of two siblings with an 8.5 Mb 6q24.2-q25.2 deletion inherited from a paternal insertion.

Similar Datasets

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