Prognostic value of X-chromosome inactivation in symptomatic female carriers of dystrophinopathy

Juan-Mateu, Jonàs; Rodríguez, Maria José; Nascimento, Andrés; Jiménez-Mallebrera, Cecilia; González-Quereda, Lidia; Rivas, Eloy; Paradas, Carmen; Madruga, Marcos; Sánchez-Ayaso, Pedro; Jou, Cristina; González-Mera, Laura; Munell, Francina; Roig-Quilis, Manuel; Rabasa, Maria; Hernández-Lain, Aurelio; Díaz-Manera, Jorge; Gallardo, Eduard; Pascual, Jordi; Verdura, Edgard; Colomer, Jaume; Baiget, Montserrat; Olivé, Montse; Gallano, Pia

doi:10.1186/1750-1172-7-82

Orphanet Journal of Rare Diseases

Table 2 Summary of genetic findings and muscle biopsy features in symptomatic carriers of DMD mutations

From: Prognostic value of X-chromosome inactivation in symptomatic female carriers of dystrophinopathy

Patient	Phenotype	DMD mutation	Muscle biopsy features	Dystrophin immunostaining	Blood DNA XCI	Muscle DNA XCI	Most inactive X-chr.	Origin of *DMD* mutation	Familial skewed XCI
1	DMD-like	Deletion exons 1–44 (c.(?_-244)_6438 + ?del, frameshift)	Severe dystrophic pattern	Generalized absence	93:7	n/p	maternal	paternal	yes
2	DMD-like	Subexonic deletion/insertion exon 17 (c.2095delinsTC, frameshift)	End-stage muscular dystrophy	n/p	100:0	51:49	paternal	n/p	no
3	D/BMD-like	Stop exon 8 (c.724C > T, p.Gln242X)	Severe dystrophic pattern	Generalized absence	100:0	61:39	paternal	n/p	yes
4	Severe BMD-like	Splice site exon 27 (c.3786 + 1G > A, predicted frameshift)	Moderate dystrophic pattern	Mosaic pattern	94:6	81:19	paternal	maternal	yes
5	Severe BMD-like	Deletion exon 68 (c.9808-?_9974 + ?del, frameshift)	Moderate dystrophic pattern	Mosaic pattern	69:31	n/p	maternal	n/p	yes
6	Severe BMD-like	Stop exon 41 (c.5893C > T, p.Gln1965X)	Severe dystrophic pattern	Reduction/absence in isolated fibres	74:26	52:48	n/i	n/p	yes
7	Severe BMD-like	Deletion exons 5–7 (c.265-?_649 + ?del, frameshift)	Severe dystrophic pattern	Mosaic pattern	81:19	87:12	n/p	n/p	n/p
8	Severe BMD-like	Deletion exon 44 (c.6291-?_6438 + ?del, frameshift)	Moderate dystrophic	Mosaic pattern with predominance of negative fibres	100:0	n/p	n/p	n/p	n/p
9	Mild BMD-like	Deletion exons 43–45 (c.6118-?_6614 + ?del, frameshift)	Mild dystrophic pattern	Mosaic pattern	n/i	n/p	n/p	n/p	n/p
10	Mild BMD-like	Deletion exons 45–50 (c.6439-?_7309 + ?del, frameshift)	Moderate dystrophic pattern.	Mosaic pattern	71:29	n/p	n/i	maternal	no
11	Mild BMD-like	Deletion exons 53–54 (c.7661-?_8027 + ?del, frameshift)	Mild dystrophic pattern	Reduction/absence in isolated fibres	81:19	n/p	n/i	maternal	no
12	Mild BMD-like	Duplication exons 50–55 (c.7201-?_8217 + ?dup, predicted in-frame)	n/p	n/p	n/i	n/p	n/p	maternal	n/p
13	Mild BMD-like	Splice site exon 48 (c.6913-1G > A, frameshift)	Mild dystrophic pattern	Mosaic pattern	81:19	53:47	maternal	maternal	yes
14	Mild BMD-like	Splice site exon 48 (c.6913-1G > A, frameshift)	n/p	n/p	72:28	n/p	paternal	maternal	yes
15	Mild BMD-like	Deletion exons 48–50 (c.6913-?_7309 + ?del, frameshift)	Mild dystrophic pattern	Mosaic pattern	52:48	40:60	n/p	n/p	n/p
16	DCM	Deletion exon 44 (c.6291-?_6438 + ?del, frameshift)	n/p	n/p	99:1	n/p	n/i	n/p	Yes
17	DCM	Deletion exons 46–52 (c.6615-?_7660 + ?del, frameshift)	n/p	n/p	63:37	n/p	n/p	n/p	n/p
18	Behavioural issues	Duplication exons 13–27 (c.1483-?_3786 + ?dup, predicted in-frame)	Myopathic changes	Normal	99:1	97:3	paternal	maternal	Yes
19	MR	Subexonic deletion exon 46 (c.6638delT, frameshift)	Myopathic changes	Absence in isolated fibres	88:12	69:31	paternal	maternal	yes
20	MR	Deletion exons 46–55 (c.6615-?_8217 + ?del, frameshift)	n/p	n/p	100:0	n/p	paternal	maternal	n/i
21	Myalgia	Duplication exons 38–43 (c.5326-?_6290 + ?dup, predicted frameshift)	n/p	n/p	74:26	n/p	paternal	maternal	yes
22	Myalgia	Deletion exons 10–43 (c.961-?_6290 + ?del, frameshift)	n/p	n/p	51:49	n/p	n/p	n/p	n/p
23	Myalgia	Deletion exon 7 (c.531-?_649 + ?del, frameshift)	Myopathic changes	Reduction/absence in isolated fibres	78:22	n/p	n/p	n/p	n/p
24	Myalgia	Deletion exons 3–13 (c.94-?_1602 + ?del, in-frame)	Myopathic changes	Mosaic pattern	50:50	n/p	n/p	n/p	n/p

X-chromosome inactivation (XCI): skewed patterns >80:20 are in bold. n/p: not performed, n/i = non-informative AR alleles.

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ISSN: 1750-1172

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