Abstract
Mutations in POMT1 and POMT2 genes were originally identified in Walker-Warburg syndrome (WWS) and subsequently reported in patients with milder phenotypes characterised by mental retardation with or without brain abnormalities and without ocular malformations. As part of a multicentric Italian study we screened the POMT1 and POMT2 genes in 61 congenital muscular dystrophy (CMD) patients with α-dystroglycan reduction on muscle biopsy and/or clinical and radiological findings suggestive of the known forms of CMD with α-dystroglycan deficiency. The aim of the study was to establish how frequently mutations in POMT1 and POMT2 occur in CMD patients in the Italian population and to evaluate the spectrum of associated phenotypes. Thirteen patients showed mutations in POMT1 and five harboured mutations in POMT2, accounting for a total of 20 different mutations, eight of which were novel (two in POMT1 and six in POMT2). Normal brain MRI associated with mental retardation and microcephaly was the most frequent finding in patients with mutations in POMT1 (six out of 13), but was also found in a patient with POMT2 mutations. Predominant cerebellar hypoplasia was also frequent both in patients with POMT1 (three out of 13) and POMT2 (three out of 5) mutations. A MEB phenotype with frontal cortical dysplasia and pons abnormalities was found in two patients with POMT1 and in one with POMT2 mutations, while a WWS phenotype was only found in a case with mutations in POMT1. Mutations causing frameshifts and stop codons were responsible for the more severe phenotypes. Our results provide further evidence that, as previously reported for FKRP, the array of mutations in POMT1 and POMT2 is ample and the spectrum of associated phenotypes is wider than initially thought.
| Original language | English |
|---|---|
| Pages (from-to) | 565-571 |
| Number of pages | 7 |
| Journal | Neuromuscular Disorders |
| Volume | 18 |
| Issue number | 7 |
| DOIs | |
| Publication status | Published - Jul 2008 |
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Keywords
- Alpha-dystroglycanopathy
- Congenital muscular dystrophy
- Mental retardation
- POMT1
- POMT2
ASJC Scopus subject areas
- Clinical Neurology
- Pediatrics, Perinatology, and Child Health
- Developmental Neuroscience
- Neurology
Cite this
POMT1 and POMT2 mutations in CMD patients : A multicentric Italian study. / Messina, S.; Mora, M.; Pegoraro, E.; Pini, A.; Mongini, T.; D'Amico, A.; Pane, M.; Aiello, C.; Bruno, C.; Biancheri, R.; Berardinelli, A.; Boito, C.; Farina, L.; Morandi, L.; Moroni, I.; Pezzani, R.; Pichiecchio, A.; Ricci, E.; Ruggieri, A.; Saredi, S.; Scuderi, C.; Tessa, A.; Toscano, A.; Tortorella, G.; Trevisan, C. P.; Uggetti, C.; Santorelli, F. M.; Bertini, E.; Mercuri, E.
In: Neuromuscular Disorders, Vol. 18, No. 7, 07.2008, p. 565-571.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - POMT1 and POMT2 mutations in CMD patients
T2 - A multicentric Italian study
AU - Messina, S.
AU - Mora, M.
AU - Pegoraro, E.
AU - Pini, A.
AU - Mongini, T.
AU - D'Amico, A.
AU - Pane, M.
AU - Aiello, C.
AU - Bruno, C.
AU - Biancheri, R.
AU - Berardinelli, A.
AU - Boito, C.
AU - Farina, L.
AU - Morandi, L.
AU - Moroni, I.
AU - Pezzani, R.
AU - Pichiecchio, A.
AU - Ricci, E.
AU - Ruggieri, A.
AU - Saredi, S.
AU - Scuderi, C.
AU - Tessa, A.
AU - Toscano, A.
AU - Tortorella, G.
AU - Trevisan, C. P.
AU - Uggetti, C.
AU - Santorelli, F. M.
AU - Bertini, E.
AU - Mercuri, E.
PY - 2008/7
Y1 - 2008/7
N2 - Mutations in POMT1 and POMT2 genes were originally identified in Walker-Warburg syndrome (WWS) and subsequently reported in patients with milder phenotypes characterised by mental retardation with or without brain abnormalities and without ocular malformations. As part of a multicentric Italian study we screened the POMT1 and POMT2 genes in 61 congenital muscular dystrophy (CMD) patients with α-dystroglycan reduction on muscle biopsy and/or clinical and radiological findings suggestive of the known forms of CMD with α-dystroglycan deficiency. The aim of the study was to establish how frequently mutations in POMT1 and POMT2 occur in CMD patients in the Italian population and to evaluate the spectrum of associated phenotypes. Thirteen patients showed mutations in POMT1 and five harboured mutations in POMT2, accounting for a total of 20 different mutations, eight of which were novel (two in POMT1 and six in POMT2). Normal brain MRI associated with mental retardation and microcephaly was the most frequent finding in patients with mutations in POMT1 (six out of 13), but was also found in a patient with POMT2 mutations. Predominant cerebellar hypoplasia was also frequent both in patients with POMT1 (three out of 13) and POMT2 (three out of 5) mutations. A MEB phenotype with frontal cortical dysplasia and pons abnormalities was found in two patients with POMT1 and in one with POMT2 mutations, while a WWS phenotype was only found in a case with mutations in POMT1. Mutations causing frameshifts and stop codons were responsible for the more severe phenotypes. Our results provide further evidence that, as previously reported for FKRP, the array of mutations in POMT1 and POMT2 is ample and the spectrum of associated phenotypes is wider than initially thought.
AB - Mutations in POMT1 and POMT2 genes were originally identified in Walker-Warburg syndrome (WWS) and subsequently reported in patients with milder phenotypes characterised by mental retardation with or without brain abnormalities and without ocular malformations. As part of a multicentric Italian study we screened the POMT1 and POMT2 genes in 61 congenital muscular dystrophy (CMD) patients with α-dystroglycan reduction on muscle biopsy and/or clinical and radiological findings suggestive of the known forms of CMD with α-dystroglycan deficiency. The aim of the study was to establish how frequently mutations in POMT1 and POMT2 occur in CMD patients in the Italian population and to evaluate the spectrum of associated phenotypes. Thirteen patients showed mutations in POMT1 and five harboured mutations in POMT2, accounting for a total of 20 different mutations, eight of which were novel (two in POMT1 and six in POMT2). Normal brain MRI associated with mental retardation and microcephaly was the most frequent finding in patients with mutations in POMT1 (six out of 13), but was also found in a patient with POMT2 mutations. Predominant cerebellar hypoplasia was also frequent both in patients with POMT1 (three out of 13) and POMT2 (three out of 5) mutations. A MEB phenotype with frontal cortical dysplasia and pons abnormalities was found in two patients with POMT1 and in one with POMT2 mutations, while a WWS phenotype was only found in a case with mutations in POMT1. Mutations causing frameshifts and stop codons were responsible for the more severe phenotypes. Our results provide further evidence that, as previously reported for FKRP, the array of mutations in POMT1 and POMT2 is ample and the spectrum of associated phenotypes is wider than initially thought.
KW - Alpha-dystroglycanopathy
KW - Congenital muscular dystrophy
KW - Mental retardation
KW - POMT1
KW - POMT2
UR - http://www.scopus.com/inward/record.url?scp=46449124425&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=46449124425&partnerID=8YFLogxK
U2 - 10.1016/j.nmd.2008.04.004
DO - 10.1016/j.nmd.2008.04.004
M3 - Article
VL - 18
SP - 565
EP - 571
JO - Neuromuscular Disorders
JF - Neuromuscular Disorders
SN - 0960-8966
IS - 7
ER -