Unbalanced whole arm translocation resulting in loss of 18p in dystonia

Nasir, Jamal; Frima, Nafsika; Pickard, Ben; Malloy, M. P.; Zhan, Lingping; Grünewald, Richard A.

doi:10.1002/mds.20846

Cited by 22 publications

(21 citation statements)

References 23 publications

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“…On the other hand, dystonia is a rare finding among these patients 5 . Up to now, only six cases have been reported, three associated with abnormalities of the white matter as in our patient 2,[6][7][8] . Cerebral abnormalities usually described in these individuals include agenesis of corpus callosum, holoprosencephaly and arhinocephaly 5 .…”

Section: Discussionmentioning

confidence: 59%

“…Up to now, at least 15 different loci (DYT1-DYT15) have been described in this condition 1,2 . Adult-onset idiopathic torsion dystonia affecting specific parts of the body, such as the eye (blepharospasm), neck (cervical dystonia), and hand (writer's cramp) has been associated with the DYT7 locus, located in the short arm of chromosome 18 [1][2][3] . Autoimmune diseases have been considered conditions associated with reactions of the immune system against selfantigens or body systems.…”

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confidence: 99%

“…It can be classified according to the distribution of affected body parts, age of onset and etiology 1 . Up to now, at least 15 different loci (DYT1-DYT15) have been described in this condition 1,2 . Adult-onset idiopathic torsion dystonia affecting specific parts of the body, such as the eye (blepharospasm), neck (cervical dystonia), and hand (writer's cramp) has been associated with the DYT7 locus, located in the short arm of chromosome 18 [1][2][3] .…”

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confidence: 99%

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Dystonia, autoimmune disease and cerebral white matter abnormalities in a patient with 18p deletion

Graziadio

Rosa

Zen

et al. 2009

Arq. Neuro-Psiquiatr.

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Dystonia is a clinically and genetically heterogeneous disorder of movement characterized by involuntary and sustained muscle contractions and rigid postures affecting one or more sites of the body. It can be classified according to the distribution of affected body parts, age of onset and etiology 1 . Up to now, at least 15 different loci (DYT1-DYT15) have been described in this condition 1,2 . Adult-onset idiopathic torsion dystonia affecting specific parts of the body, such as the eye (blepharospasm), neck (cervical dystonia), and hand (writer's cramp) has been associated with the DYT7 locus, located in the short arm of chromosome 18 [1][2][3] . Autoimmune diseases have been considered conditions associated with reactions of the immune system against selfantigens or body systems. They are disorders often associated with severe and chronic morbidity. In spite of recent advances, much of their etiology is still unknown 4 . We describe a rare case of a patient with 18p deletion syndrome presenting focal dystonia, Hashimoto thyroiditis, vitiligo and cerebral white matter abnormalities. CaSeThe patient is a 30 year old white woman, the fourth child of a non-consanguineous couple, without any history of similar cases in the family. The patient was born full-term, with a Cesarean section, after a pregnancy without intercurrences. During her first year of life, she had several episodes of infection (otitis and tonsillitis) as well as constipation where laxative use was needed. At 3 months, she had a convulsive crisis during fever. In relation to her neuropsychomotor development, the mother recalls she supported her own head at 6 months and pronounced her first words at the age of three. The patient was also unable to accompany normal school, failing several grades. After a long period without intercurrences, she began with blepharospasm together with cervical dystonia. She presented telarche at the age of 12 and menarche at 13, and at around 20 she began with menstrual irregularity. The hormonal evaluation conducted later diagnosed hypothyroidism due to Hashimoto thyroiditis.During the physical exam at the age of 30, she presented obesity (weighing 70 kg, between the 90-97 percentiles), short stature (149 cm, under the 3 percentile), brachycephaly, but without microcephalia (head circumference of 53 cm -between the 2-50 percentiles), rounded face, ocular hypertelorism (interpupillary distance higher than the 97 percentile), ptosis, blepharospasm, corneal opacification, hypoplasia of the middle third of the face, broad nasal bridge, high palate, short and broad neck, low posterior hairline, broad thorax and accentuated cervical kyphosis ( Figs 1A and B). She also had dextroconvex thoracic scoliosis, small hands and feet with hyperconvex nails (Figs 1C and D) and achromic spots of different sizes, spread about the body (thorax, dorsum and members), and vitiligo was diagnosed. The face remained in a fixed position, always turned to the right and downwards (Figs 1A and B). Nuclear magnetic resonance of the skull reveal...

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Section: Discussionmentioning

confidence: 59%

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confidence: 99%

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confidence: 99%

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Dystonia, autoimmune disease and cerebral white matter abnormalities in a patient with 18p deletion

Graziadio

Rosa

Zen

et al. 2009

Arq. Neuro-Psiquiatr.

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“…Whole gene deletions were excluded in 300/366 patients and duplications in 129/366, suggesting that AFG3L2 deletions/duplications are not common in ADCAs. Moreover, two related patients with an 18p deletion encompassing AFG3L2 reportedly have not developed ataxia [Nasir et al, 2006]. Copy number variants encompassing part or whole of AFG3L2 gene exist in normal individuals [Kim et al, 2009;Redon et al, 2006].…”

Section: Discussionmentioning

confidence: 97%

Missense mutations in the AFG3L2 proteolytic domain account for ∼1.5% of European autosomal dominant cerebellar ataxias

et al. 2010

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Spinocerebellar ataxia type 28 is an autosomal dominant form of cerebellar ataxia (ADCA) caused by mutations in AFG3L2, a gene that encodes a subunit of the mitochondrial m-AAA protease. We screened 366 primarily Caucasian ADCA families, negative for the most common triplet expansions, for point mutations in AFG3L2 using DHPLC. Whole-gene deletions were excluded in 300 of the patients, and duplications were excluded in 129 patients. We found six missense mutations in nine unrelated index cases (9/366, 2.6%): c.1961C>T (p.Thr654Ile) in exon 15, c.1996A>G (p.Met666Val), c.1997T>G (p.Met666Arg), c.1997T>C (p.Met666Thr), c.2011G>A (p.Gly671Arg), and c.2012G>A (p.Gly671Glu) in exon 16. All mutated amino acids were located in the C-terminal proteolytic domain. In available cases, we demonstrated the mutations segregated with the disease. Mutated amino acids are highly conserved, and bioinformatic analysis indicates the substitutions are likely deleterious. This investigation demonstrates that SCA28 accounts for ∼3% of ADCA Caucasian cases negative for triplet expansions and, in extenso, to ∼1.5% of all ADCA. We further confirm both the involvement of AFG3L2 gene in SCA28 and the presence of a mutational hotspot in exons 15-16. Screening for SCA28, is warranted in patients who test negative for more common SCAs and present with a slowly progressive cerebellar ataxia accompanied by oculomotor signs.

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“…The GNAL gene is located on the short arm of chromosome 18p11, and the absence of GNAL may contribute to dystonia in patients with the 18p deletion syndrome. 3 Onset among mutation carriers occurred mainly in the neck (82%) at a mean age at onset of 31.3 (range, 7-54) years. On examination, almost all patients had cervical dystonia (93%), but cranial (57%) and speech involvement (44%) were also quite common.…”

Section: Introductionmentioning

confidence: 99%