Angelika Köhler

Duplication or insertion in 15q11-13 associated with mental retardation-short stature and obesity-Prader-Willi or Cohen syndrome?

Difficulties of differential diagnosis between Prader‐Willi Syndrome and Cohen Syndrome are demonstrated in a 12–year‐old girl with obesity and mental retardation.

Assignment of genes encoding GABAA receptor subunits alpha 1, alpha 6, beta 2, and gamma 2 to a YAC contig of 5q33.

A gene cluster consisting of the four γ-aminobutyric acidA (GABAA) receptor subunit genes GABRA1, GABRA6, GABRB2, and GABRG2 was assigned to a yeast artificial chromosome (YAC) contig of 5q33. Two of the 26 YACs of the contig are positive for all four subunit genes. The order of the GABR sub-unit genes with respect to known anonymous gene loci is cen — D5S380 — D5S403 — D5S529 — GABRB2 — GABRA1/A6 — GABRG2 — D5S422 — tel. This novel YAC contig lies between known YAC contigs of 5q34/q35 and 5q31-q33.

DYT7 Gene Locus for Cervical Dystonia on Chromosome 18p Is Questionable

A locus implicated in autosomal dominant cervical dystonia was assigned to chromosome 18p in 1 large family more than 15 years ago. This locus was designated DYT7. We reanalyzed the family clinically and genetically.

Plasmolipin: genomic structure, chromosomal localization, protein expression pattern, and putative association with Bardet-Biedl syndrome

Abstract. Plasmolipin is a membrane protein and belongs to the tetraspan molecule (4TM) family, an expanding group of myelin proteins many of which could be linked to human hereditary demyelinating neuropathies. We have cloned and sequenced the mouse plasmolipin gene, revealing the common organization of the 4TM gene group with four exons and a large first intron. Western blot analysis with an antibody raised against the C-terminal intracellular part of the protein showed that plasmolipin is expressed not only in the nervous system and kidney, but also in a number of other tissues such as thymus, testis, lung, and thyroid gland. By means of radiation hybrid mapping and FISH analysis, we could localize the human plasmolipin gene to Chromosome 16q13 within the putative region of the Bardet-Biedl syndrome type 2 (BBS2) gene locus. BBS2 is a clinically and genetically heterogeneous group of disorders resulting in rod-cone dystrophy, obesity, postaxial polydactyly, renal dysfunction, and mental retardation, which were very recently associated with a novel gene designated BBS2. With respect to intrafamiliar variations in the manifestation of BBS, we suggest that plasmolipin might be either another candidate gene or a modifier of the BBS2 phenotype.

Benign infantile convulsions (IC) and subsequent paroxysmal kinesigenic dyskinesia (PKD) in a patient with 16p11.2 microdeletion syndrome

Paroxysmal kinesigenic dyskinesia with infantile convulsions (PKD/IC) is caused by mutations in the gene PRRT2 located in 16p11.2. A deletion syndrome 16p11.2 is well established and is characterized by intellectual disability, speech delay, and autism. PKD/IC, however, is extremely rare in this syndrome. We describe a case of PKD/IC and 16p11.2 deletion syndrome and discuss modifiers of PRRT2 activity to explain the rare concurrence of both syndromes.

Integrated physical and transcript map of 5q31.3-qter

We have constructed a physical and transcript map of 5q31.3-qter. The contig comprises 173 yeast artificial chromosomes (YACs) to which 159 sequence tagged sites (STSs), 47 expressed sequence tags (ESTs), and 32 genes were assigned. Previously published partial YAC contigs of the region have been refined and integrated. Given that the region contains 25 Mbp of DNA the average spacing of markers is approximately 100 kb.

Polyneuropathy, scoliosis, tall stature, and oligodontia represent novel features of the interstitial 6p deletion phenotype†‡

Birgit Zirn,* Maja Hempel, Andreas Hahn, Bernd Neubauer, Janine Wagenstaller, Núria Rivera-Bruguès, Tim Matthias Strom, and Angelika Köhler Institute of Human Genetics, University of Giessen, Giessen, Germany Institute of Human Genetics, Technische Universität München, Munich, Germany Department of Neuropediatrics, University of Giessen, Giessen, Germany HelmholtzZentrum München, Neuherberg, Germany

8p23.1 duplication syndrome: narrowing of critical interval to 1.80 Mbp

BackgroundA 3.68 Mbp duplication of 8p23.1 defines the 8p23.1 duplication syndrome. The main features of this syndrome are developmental delay and/or learning problems.ResultsHere we present a patient with a 1.80 Mbp duplication in 8p23.1 and characteristic signs and symptoms of the syndrome, including delay of motor and speech development and intellectual disability.DiscussionThe case indicates that genes within this interval, in particular dosage sensitive genes SOX7 and TNKS1, and possibly MIR124-1 and MIR598 as well suffice to cause the pathognomonic features of the 8p23.1 duplication syndrome.

Clinical and molecular genetic findings in five patients with Miller-Dieker syndrome

Five patients with type 1 lissencephaly, typical features of Miller‐Dieker syndrome and apparently normal karyotypes were investigated for microdeletions in chromosome 17p13.3. Analysis of loci D17S5 and D17S379 by polymerase chain reaction and fluorescence in situ hybridization revealed a deletion in three cases. No deletion was observed in the remaining two cases. Given the almost identical clinical picture of the five patients, the great variation in the molecular findings argues against Miller‐Dieker syndrome being a contiguous gene syndrome.

Reply to Dr. Hoo

Kousseff, B. G. (1980). Chromosomal abnormality in Prader-Willi syndrome. Clin. Genet. 17, 364366. Ledbetter, D. H., J. T. Mascarello, V. M. Riccardi, V. D. Harper, S. D. Airhart & R. J. Strobel (1982). Chromosome 15 abnormalities and the Prader-Willi syndrome: a follow-up report of 40 cases. Am. J. Hum. Genet. 34,278285. Michaelsen, K. F., C. Lundsteen & F. J. Hansen (1979). Prader-Willi syndrome and chromosomal mosaicism 46,XY/47,XY, +mar in two cases. Clin. Genet. 16, 147-150. Morton, C. C., J. A. Brown, G. A. Evans, W. E. Nance, T. Mohanakumar & I. R. Kirsch (1982). Detection and localization of an extra HLA locus in a karyotypically normal male by chromosomal in situ hybridization. Am. J . Hum. Genet. 34, 136A. Motegi, T. (1982). High rate of detection of 13q14 deletion mosaicism among retinoblastoma patients (using more extensive methods). Hum. Genet. 61, 95-97. Smith, A. & M. Noel (1980). A girl with the Prader-Willi syndrome and Robertsonian translocation 45,XX,t(14; 15) (pl1 ; q l l ) which was present in three normal family members. Hum. Genet. 55, 271-273. Winsor, E. J. T. & J. P. Welch (1983). PraderWilli syndrome associated with inversion of chromosome 15. Clin. Genet. 24, 45-61. Wisniewski, L., T. Hassold, J. Heffelfinger & J. V. Higgins (1979). Cytogenetic and clinical studies in five cases of inv dup( 15). Hum. Genet. 50,