Browsing by Person "Paracchini, Silvia"

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CMIP and ATP2C2 Modulate Phonological Short-Term Memory in Language Impairment
(2009-08-14) Newbury, D. F.; Winchester, Laura; Addis, L.; Paracchini, Silvia; Buckingham, Lyn-Louise; Clark, Ann; Cohen, W.; Cowie, H.; Dworzynski, Katharina; Everitt, Andrea; Goodyer, I. M.; Hennessy, E.; Kindley, A. D.; Miller, Laura L.; Nasir, J.; O'Hare, Anne; Shaw, D.; Simkin, Z.; Simonoff, E.; Slonims, V.; Watson, Jocelynne; Ragoussis, Jiannis; Fisher, S. E.; Seckl, J.; Helms, P. J.; Bolton, P. F.; Pickles, A.; Conti-Ramsden, G.; Baird, G.; Bishop, DVM; Monaco, A. P.
Specific language impairment (SLI) is a common developmental disorder characterized by difficulties in language acquisition despite otherwise normal development and in the absence of any obvious explanatory factors. We performed a high-density screen of SLI1, a region of chromosome 16q that shows highly significant and consistent linkage to nonword repetition, a measure of phonological short-term memory that is commonly impaired in SLI. Using two independent language-impaired samples, one family-based (211 families) and another selected from a population cohort on the basis of extreme language measures (490 cases), we detected association to two genes in the SLI1 region: that encoding c-maf-inducing protein (CMIP, minP = 5.5 10-7 at rs6564903) and that encoding calcium-transporting ATPase, type2C, member2 (ATP2C2, minP = 2.0 10-5 at rs11860694). Regression modeling indicated that each of these loci exerts an independent effect upon nonword repetition ability. Despite the consistent findings in language-impaired samples, investigation in a large unselected cohort (n = 3612) did not detect association. We therefore propose that variants in CMIP and ATP2C2 act to modulate phonological short-term memory primarily in the context of language impairment. As such, this investigation supports the hypothesis that some causes of language impairment are distinct from factors that influence normal language variation. This work therefore implicates CMIP and ATP2C2 in the etiology of SLI and provides molecular evidence for the importance of phonological short-term memory in language acquisition.
Increased prevalence of sex chromosome aneuploidies in specific language impairment and dyslexia.
(Wiley, 2014-04) Simpson, Nuala H.; Addis, Laura; Brandler, William M.; Slonims, Vicky; Clark, Ann; Watson, Jocelynne; Scerri, Thomas S.; Hennessy, Elizabeth R.; Bolton, Patrick F.; Conti-Ramsden, Gina; Fairfax, Benjamin P.; Knight, Julian C.; Stein, John; Talcott, Joel B.; O'Hare, Anne; Baird, Gillian; Paracchini, Silvia; Fisher, Simon E.; Newbury, Dianne F.; Consortium, Sli
AIM Sex chromosome aneuploidies increase the risk of spoken or written language disorders but individuals with specific language impairment (SLI) or dyslexia do not routinely undergo cytogenetic analysis. We assess the frequency of sex chromosome aneuploidies in individuals with language impairment or dyslexia. METHOD Genome-wide single nucleotide polymorphism genotyping was performed in three sample sets: a clinical cohort of individuals with speech and language deficits (87 probands: 61 males, 26 females; age range 4 to 23 years), a replication cohort of individuals with SLI, from both clinical and epidemiological samples (209 probands: 139 males, 70 females; age range 4 to 17 years), and a set of individuals with dyslexia (314 probands: 224 males, 90 females; age range 7 to 18 years). RESULTS In the clinical language-impaired cohort, three abnormal karyotypic results were identified in probands (proband yield 3.4%). In the SLI replication cohort, six abnormalities were identified providing a consistent proband yield (2.9%). In the sample of individuals with dyslexia, two sex chromosome aneuploidies were found giving a lower proband yield of 0.6%. In total, two XYY, four XXY (Klinefelter syndrome), three XXX, one XO (Turner syndrome), and one unresolved karyotype were identified. INTERPRETATION The frequency of sex chromosome aneuploidies within each of the three cohorts was increased over the expected population frequency (approximately 0.25%) suggesting that genetic testing may prove worthwhile for individuals with language and literacy problems and normal non-verbal IQ. Early detection of these aneuploidies can provide information and direct the appropriate management for individuals.