BACKGROUND: Chromosome 22q13 has shown linkage with schizophrenia (SCZ) and bipolar affective disorder (BPAD). A missense mutation in MLC1 (putative cation-channel gene on 22q13) co-segregating with periodic catatonic schizophrenia has been reported. We have investigated the relationship of MLC1 with SCZ and BPAD in Southern India. METHODS: All exons and flanking intronic sequences of MLC1 were screened for novel variations. Case-control (216 BPAD, 193 SCZ, 116 control subjects) and family-based analyses (113 BPAD, 107 SCZ families) were performed to evaluate association of MLC1 with these disorders. RESULTS: We found 33 MLC1 sequence variations, including three novel mutations: Val210Ile, Leu308Gln, and Arg328His in six BPAD cases and Val210Ile in one control individual. Minor allele of a common variation, ss16339182 (in approximately 6 Kb Linkage-Disequilibrium [LD]-block) was associated with BPAD in case-control (p = .03) and family-based analyses (transmitted/nontransmitted [T/NT]-44/20; p = .003). Association was observed for rs2235349 and rs2076137 with SCZ and ss16339163 with BPAD in case-control study. Using Block 2 haplotype tagging single nucleotide polymorphisms (htSNPs), GC haplotype revealed association (p = .02) and excess transmission (p = .002) with BPAD. CONCLUSIONS: Association of MLC1 with SCZ and BPAD suggests involvement of a common pathway. Rare missense mutations and common variants associated with BPAD favors hypothesis about likely involvement of both rare and common polymorphisms in etiology of this complex disorder.
BACKGROUND: Chromosome 22q13 has shown linkage with schizophrenia (SCZ) and bipolar affective disorder (BPAD). A missense mutation in MLC1 (putative cation-channel gene on 22q13) co-segregating with periodic catatonic schizophrenia has been reported. We have investigated the relationship of MLC1 with SCZ and BPAD in Southern India. METHODS: All exons and flanking intronic sequences of MLC1 were screened for novel variations. Case-control (216 BPAD, 193 SCZ, 116 control subjects) and family-based analyses (113 BPAD, 107 SCZ families) were performed to evaluate association of MLC1 with these disorders. RESULTS: We found 33 MLC1 sequence variations, including three novel mutations: Val210Ile, Leu308Gln, and Arg328His in six BPAD cases and Val210Ile in one control individual. Minor allele of a common variation, ss16339182 (in approximately 6 Kb Linkage-Disequilibrium [LD]-block) was associated with BPAD in case-control (p = .03) and family-based analyses (transmitted/nontransmitted [T/NT]-44/20; p = .003). Association was observed for rs2235349 and rs2076137 with SCZ and ss16339163 with BPAD in case-control study. Using Block 2 haplotype tagging single nucleotide polymorphisms (htSNPs), GC haplotype revealed association (p = .02) and excess transmission (p = .002) with BPAD. CONCLUSIONS: Association of MLC1 with SCZ and BPAD suggests involvement of a common pathway. Rare missense mutations and common variants associated with BPAD favors hypothesis about likely involvement of both rare and common polymorphisms in etiology of this complex disorder.
Authors: H Wang; S Duan; J Du; X Li; Y Xu; Z Zhang; Y Wang; G Huang; G Feng; L He Journal: J Neural Transm (Vienna) Date: 2006-01-25 Impact factor: 3.575
Authors: Julie Gauthier; Nathalie Champagne; Ronald G Lafrenière; Lan Xiong; Dan Spiegelman; Edna Brustein; Mathieu Lapointe; Huashan Peng; Mélanie Côté; Anne Noreau; Fadi F Hamdan; Anjené M Addington; Judith L Rapoport; Lynn E Delisi; Marie-Odile Krebs; Ridha Joober; Ferid Fathalli; Fayçal Mouaffak; Ali P Haghighi; Christian Néri; Marie-Pierre Dubé; Mark E Samuels; Claude Marineau; Eric A Stone; Philip Awadalla; Philip A Barker; Salvatore Carbonetto; Pierre Drapeau; Guy A Rouleau Journal: Proc Natl Acad Sci U S A Date: 2010-04-12 Impact factor: 11.205
Authors: A Denayer; H Van Esch; T de Ravel; J-P Frijns; G Van Buggenhout; A Vogels; K Devriendt; J Geutjens; P Thiry; A Swillen Journal: Mol Syndromol Date: 2012-05-16