Facioscapulohumeral Muscular Dystrophy: From Clinical Data to Molecular Genetics and Return

Salani, Monica; Morini, Elisabetta; Scionti, Isabella; Tupler, Rossella

doi:10.5772/28864

Cited by 2 publications

(4 citation statements)

References 152 publications

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“…Of them, one subject (FSHD18_I:2) carried a short 4qB allele, which is not permissive for FSHD, whereas the other individuals displayed a short 4qA allele <10 RU, representing thereby non‐penetrant gene carriers. Interestingly, most of them (18/20) were females, in line with previous studies reporting a higher proportion of women among the asymptomatic/unaffected carriers 8–19 . The non‐penetrant gene carriers showed an average age of 60 years, except for 3 younger (<35 years of age) subjects (FSHD51_II:2, FSHD68_II:1, and FSHD100_II:2) that should be monitored to rule out the manifestation of FSHD later in life.…”

Section: Resultssupporting

confidence: 84%

“…Interestingly, most of them (18/20) were females, in line with previous studies reporting a higher proportion of women among the asymptomatic/unaffected carriers. [8][9][10][11][12][13][14][15][16][17][18][19] The nonpenetrant gene carriers showed an average age of 60 years, except for 3 younger (<35 years of age) subjects (FSHD51_II:2, FSHD68_II:1, and FSHD100_II:2) that should be monitored to rule out the manifestation of FSHD later in life.…”

Section: Resultsmentioning

confidence: 99%

“…The formula was derived from Salani et al 15 For FSHD1, the threshold for assessing the presence of DRA was fixed at D4Z4 size ≤43 kb, which corresponds to ≤10 RU. However, patients reporting D4Z4 size ranging from 11 and 20 RU were also reported, because this size range is usually found in FSHD2 cases.…”

Section: Methodsmentioning

confidence: 99%

“…The characterization of 4qA and 4qB allelic variants was performed by an additional hybridization with specific probes according to standard procedures. The number of RU was estimated considering the size of the EcoRI fragments (kb) and the formula reported below:

Number of Repeated Units = \frac{([], EcoRI fragment length ((), kb) - ((), 8.6 kb))}{3.3 kb} .

The formula was derived from Salani et al 15 For FSHD1, the threshold for assessing the presence of DRA was fixed at D4Z4 size ≤43 kb, which corresponds to ≤10 RU. However, patients reporting D4Z4 size ranging from 11 and 20 RU were also reported, because this size range is usually found in FSHD2 cases.…”

Section: Methodsmentioning

confidence: 99%

See 3 more Smart Citations

Characterization of D4Z4 alleles and assessment of de novo cases in Facioscapulohumeral dystrophy (FSHD) in a cohort of Italian families

Strafella,

Colantoni,

Megalizzi

et al. 2023

Clinical Genetics

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Facioscapulohumeral dystrophy (FSHD) is an autosomal dominant disease, although 10%–30% of cases are sporadic. However, this percentage may include truly de novo patients (carrying a reduced D4Z4 allele that is not present in either of the parents) and patients with apparently sporadic disease resulting from mosaicism, non‐penetrance, or complex genetic situations in either patients or parents. In this study, we characterized the D4Z4 Reduced Alleles (DRA) and evaluated the frequency of truly de novo cases in FSHD1 in a cohort of DNA samples received consecutively for FSHD‐diagnostic from 100 Italian families. The D4Z4 testing revealed that 60 families reported a DRA compatible with FSHD1 (1–10 RU). The DRA co‐segregated with the disease in most cases. Five families with truly de novo cases were identified, suggesting that this condition may be slightly lower (8%) than previously reported. In addition, D4Z4 characterization in the investigated families showed 4% of mosaic cases and 2% with translocations. This study further highlighted the importance of performing family studies for clarifying apparently sporadic FSHD cases, with significant implications for genetic counseling, diagnosis, clinical management, and procreative choices for patients and families.

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Section: Resultssupporting

confidence: 84%