In a large consanguineous Bedouin family with bilateral frontoparietal polymicrogyria, Piao et al. (2004) identified a C-T transition at nucleotide 1693 of the GPR56 gene, resulting in the substitution of the conserved amino acid (R565W). This pedigree consisted of two nuclear families that were distant related to one another; the two affected individuals from the first family had first-cousin parents, and the affected individual from the second family had consanguineous parents whose exact relationship was unknown. In addition, in one child, born to first cousin Arab parents, with bilateral frontoparietal polymicrogyria, Piao et al. (2004) identified homozygosity for a G-C transversion at nucleotide 272 of exon 3 of the GPR56 gene, resulting in a cysteine-serine substitution at codon 91 (C91S).

Straussberg et al. (1996) described a Palestinian family in which the parents were first cousins and three of the siblings suffered from moderate mental retardation, pachygyria and strabismus. In 2002, Piao et al. described the clinical and genetic features of the autosomal recessive stereotyped form of polymicrogyria in two consanguineous families from Palestine. The first pedigree was originally reported by Straussberg et al. (1996) and was described as having pachygyria. The second pedigree came from the same village as the first, although there was no known relationship between the two families. A genome-wide linkage screen revealed a single locus that was identical by descent in affected children in both families and showed a single disease-associated haplotype, suggesting a common founder mutation. The locus for bilateral frontoparietal polymicrogyria mapped to chromosome 16q12.2-21, with a minimal interval of 17 cM.

Chang et al. (2003) reported 19 patients from 10 kindreds with apparent autosomal recessive bilateral frontoparietal polymicrogyria. Included were the 2 families reported previously by Piao et al. (2002). Chang et al. (2003) also conducted linkage analysis and mapped the disease to a locus at 16q12-q21.

In 2004, Piao et al. identified a splicing mutation at the +3 position of intron 9 of the GPR56 gene, changing G>C in a consanguineous Palestinian family with three children with bilateral frontoparietal polymicrogyria , originally described by Straussberg et al. (1996). This mutation was also found in a second family from the same village with first-cousin parents and two affected children. Additionally, in two independent consanguineous Palestinian families with bilateral frontoparietal polymicrogyria, Piao et al. (2004) identified a T>A transversion at nucleotide 1036 of the GPR56 gene (1036T>A). One family had two affected children and the other had one affected child. In all cases, affected individuals were homozygous for the missense mutation (along with shared alleles at flanking microsatellite markers), representing a founder mutation. The 1036T>A mutation, found in these pedigrees, substitutes serine for the first cysteine in the cysteine box of the GPR56 protein (p.C346S). Unlike all other BFPP patients, the affected individuals from these two families also have microcephaly (characterized by a smaller than normal overall cerebral cortical size). Piao et al. (2004) explained the severe effect of this mutation is that it likely involves the posttranslational processing of the GPR56 protein. They also speculated that the C346S mutation causes microcephaly by abolishing normal cleavage of GPR56 and affecting its proper trafficking, and possibly that of other proteins.

In a consanguineous Qatari family with two children with bilateral frontoparietal polymicrogyria, Piao et al. (2004) identified a C-T transition at nucleotide 112 of the GPR56 gene, resulting in an arg-trp substitution at codon 38 (R38W) and probably affecting ligand binding by GPR56.