X-linked myotubular myopathy (XLMTM) is a congenital neuromuscular disorder defined by severe hypotonia, respiratory failure and histopathologic changes in muscle biopsy. The objective of this report is to inform about our experience of genetic analysis on a group of 25 unrelated XLMTM patients, clinically diagnosed by several Italian and European Medical Institutes from 2006 to 2015. The molecular strategy used for genotyping involved Sanger sequencing of coding and intron/exon regions and the Multiplex Ligation Probe Amplification method. A total of 13 different point variants (6 nonsense, 5 missense, 1 splicing and 1 small deletion) were found in 15 patients (60%). Three were new missense variants: c.185G>T p.(Arg62Ile), c.719T>A p.(Val240Glu), and c.1262G>T p.(Arg421Leu). No large duplications/deletions have been identified. We performed carrier testing of at-risk female relatives. Only one mutation was de novo. Successively, we offered XLMTM prenatal testing for seven pregnancies in five unrelated families. In this context, the aim to propose an effective molecular diagnostic service is to confirm clinical XLMTM diagnosis, to monitor the cause-disease mutation segregation in the family and to offer genetic counseling to have correct information regarding offspring risks and the prenatal testing.

Longo, G., Russo, S., Novelli, G., Sangiuolo, F.c., D'Apice, M.r. (2016). Mutation spectrum of the MTM1 gene in XLMTM patients: 10 years of experience in prenatal and postnatal diagnosis. CLINICAL GENETICS, 89(1), 93-98 [10.1111/cge.12674].

Mutation spectrum of the MTM1 gene in XLMTM patients: 10 years of experience in prenatal and postnatal diagnosis

NOVELLI, GIUSEPPE;SANGIUOLO, FEDERICA CARLA;D'APICE, MARIA ROSARIA
2016-09-04

Abstract

X-linked myotubular myopathy (XLMTM) is a congenital neuromuscular disorder defined by severe hypotonia, respiratory failure and histopathologic changes in muscle biopsy. The objective of this report is to inform about our experience of genetic analysis on a group of 25 unrelated XLMTM patients, clinically diagnosed by several Italian and European Medical Institutes from 2006 to 2015. The molecular strategy used for genotyping involved Sanger sequencing of coding and intron/exon regions and the Multiplex Ligation Probe Amplification method. A total of 13 different point variants (6 nonsense, 5 missense, 1 splicing and 1 small deletion) were found in 15 patients (60%). Three were new missense variants: c.185G>T p.(Arg62Ile), c.719T>A p.(Val240Glu), and c.1262G>T p.(Arg421Leu). No large duplications/deletions have been identified. We performed carrier testing of at-risk female relatives. Only one mutation was de novo. Successively, we offered XLMTM prenatal testing for seven pregnancies in five unrelated families. In this context, the aim to propose an effective molecular diagnostic service is to confirm clinical XLMTM diagnosis, to monitor the cause-disease mutation segregation in the family and to offer genetic counseling to have correct information regarding offspring risks and the prenatal testing.
4-set-2016
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore MED/03 - GENETICA MEDICA
English
MLPA; MTM1 variants; XLMTM; prenatal diagnosis
Longo, G., Russo, S., Novelli, G., Sangiuolo, F.c., D'Apice, M.r. (2016). Mutation spectrum of the MTM1 gene in XLMTM patients: 10 years of experience in prenatal and postnatal diagnosis. CLINICAL GENETICS, 89(1), 93-98 [10.1111/cge.12674].
Longo, G; Russo, S; Novelli, G; Sangiuolo, Fc; D'Apice, Mr
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/119711
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