Gene: [17p133/PAFAH1B1] platelet-activating factor acetylhydrolase, isoform Ib, alpha subunit (45kD); lissencephaly I ('smooth brain'); Miller-Dieker syndrome chromosome region (agyria-pachygyria; MIM:247200);

COM	[1] Reiner-1993 cloned cDNA for a protein containing the multiple beta-transducin-like, or WD40 (W:Trp; D:Asp) repeat units (about the repeats, see Duronio RG et al, Proteins, v.13, 41-56, 1992). The corresponding gene LIS-1 encoding this protein was mapped on the same MDS chromosome band by using a panel of monochromosomal somatic cell hybrids, FISH analysis and gDNA samples from two patients with the MDS form of lissencephaly I. Although LIS-1 revealed 'relatively low sequence similarity (55%)' to human beta-transducin (i.e., beta-subunit of G proteins), the authors speculated that the gene could possibly be involved in a signal transduction pathway likewise beta-subunits of heteromeric G proteins (FAM:GNBP/00.0). [2] Hattori-1994 cloned the cDNA for the 45 KD subunit of the brain-derived PAF acetylhydrolase (PAF is a platelet-activating factor). The amino acid sequence of the subunit revealed a striking identity with a protein encoded by the Miller-Dieker syndrome's causative gene (LIS-1) which has earlier been cloned by Reiner-1993."
MOP	There are at least two type of platelet-activating factor (PAF) acetylhydrolase, which inactivates PAF by removing the acetyl group at the sn-2 position. Isoform Ib is a heterotrimer comprising alpha (45kD), beta (30kD; see GEM:00.0/PAFAH1B2), and gamma (29kD; see GEM:00.0/PAFAH1B3) subunits. Isoform II is a 40kD monomer (see GEM:00.0/PAFAH2). See also GEM:06p/PAFAH on plasma type of PAF acetylhydrolase."
PAT	Lissencephaly (or, 'smooth' brain) designates brain either entirely without gyri (agyria) or with poorly expressed gyri (pachygyria). According to Ledbetter-1992, about 15% of patients with the isolated lissencephaly I and more than 90% MDS patients have hemizygous microdeletions in a relevant 350kb region in chromosome 17p13.3."
HET	Three clinical syndromes are known: [1] Type I Miller-Dieker lissencephaly linked with this gene locus Lissencephaly-I can occur either as an 'isolated agyria-pachygyria' or in association with multiple facial defects. [2] Type I Norman-Roberts lissencephaly (MIM:257320) in which its genetic linkage with the given gene is not proven. [3] Type II (Walker-Warburg) lissencephaly. Etiology (including gene mapping and linkage) and pathogenesis of the type II lissencephaly, also mentioned as the HARD+/-E syndrome (Hydrocephaly, Agyria, Retinal Dysplasia, with or without Encephalocele), are yet unknown although autosomal recessive inheritance is suggested (MIM:236670)."
ASS	Kwiatkowski-1990 reported that profilin gene localized to the same chromosome subsegment (GEM:17p133/PFN1) is 'part of the genetic material' deleted in some patients with Miller-Dieker lissencephaly; but other patients have smaller deletions which do not affect this gene. This means that single allelic deletions of PFN1 do not play a major role in the essential Miller-Dieker phenotype although may contribute to the clinical polymorphism of this syndrome in some patients."
REL	GEM:02p112/LIS2; GEM:02q13/LIS2P1.
REF	LOC,CYG,PAT "Bordarier C &: Hum Genet, 73, 374-378, 1986 PAT,MUT "Chong SS &: AJHG, 59, A23-23, 1996 HIS,PHE,FOG "Dieker &: (in) Clinical Delineation of Birth Defects, II: Malformation Syndromes, NY, Nat Found-M Dim, 53-64, 1969 CAG,CYG,MOL "Dobyns WB &: AJHG, 48, N3, 584-594, 1991 REV,PHE,PAT "Dobyns WB &: Am J Med Genet, 18, 509-526, 1984 LOC,CYG,PAT "Greenberg F &: Am J Med Genet, 23, 853-859, 1986 SEQ,COD,MAM "Hattori M &: Nature, 370, (21 Jul), 216-218, 1994 COM,PAT,CYG,MOL "Kwiatkowski DJ &: AJHG, 46, N3, 559-567, 1990 CAG,CYG,MOL "Ledbetter DH &: AJHG, 50, N1, 182-189, 1992 MAP "Ledbetter DH &: Genomics, 7, 264-269, 1990 HIS,PHE,FOG "Miller JQ: Neurology, 13, 841-850, 1963 PAT "Neer EJ &: Nature Genet, 5, 3-4, 1993 PEP,SEQ,COD,LOC,CYG "Reiner O &: Nature, 364, (19 Aug), 717-721, 1993 LOC,CYG,PAT "Schwartz CE &: AJHG, 43, N5, 597-604, 1988 LOC,CYG,PAT "Stratton RF &: Hum Genet, 67, 193-200, 1984 LOC,CYG,PAT "vanTuinen P &: AJHG, 43, N5, 587-596, 1988
SWI	SWISSPROT: P43034
KEY	neu, devd, face
CLA	coding, basic
LOC	17 p13.3
MIM	MIM: 601545
EZN	ENZYME: 3.1.1.47