Peretz et al. (1997) demonstrated that the Cys 618 Arg mutation in the RET gene cosegregates with familial medullary thyroid carcinoma and Hirschsprung disease in two Moroccan Jewish families in which no involvement of pheochromocytoma or parathyroidism was observed. A single haplotype shared by chromosomes bearing the Cys 618 Arg mutation in both families strongly suggested a founder effect for this mutation. Peretz et al. (1997) observed in several other previously reported families, an excess of maternal over paternal mutated RET alleles in offsprings affected by Hirschsprung disease, probably because of parental imprinting.

Benazzouz et al. (2006) identified the first RET mutation underlying multiple endocrine neoplasia type IIA (NEM2A) in Morocco. The C634Y mutation was present in the heterozygous state in a Moroccan family with MEN2A. Genetic screening showed that six asymptomatic members of this family were not C364Y carriers.

Zirie et al. (2001) studied the pattern of multiple endocrine neoplasia type IIA (MEN2A) and described the clinical features and results of genetic testing and treatment in 21 members of the first reported family with MEN2A in Qatar. Ten members in this kindred (6 adults and 4 children) were affected with MEN2A. The proband was a 27-year old Qatari female, who presented with a 3-4 year history of goiter. Her grandfather had had multiple tumors removed from the neck and abdomen. DNA analysis revealed a RET proto-oncogene mutation in codon 634 (TGC-GGC), which was also seen in her mother. All 21 family members of the proband were screened with genetic testing for the RET proto-oncogene mutation. Those subjects with the mutation were further assessed for pheochromocytoma by measurement of the 24-hour urinary vanillylmandelic acid, metanephrines, and catecholamines, and those with high levels underwent a metaiodobenzylguanidine scan and adrenalectomy. The serum calcium was measured as an effort to detect hyperparathyroidism. Those family members who had the mutation and were eligible for surgical treatment underwent total thyroidectomy and central compartment dissection. In those patients with high postoperative calcitonin levels, residual disease was sought with radiologic imaging, and follow-up was done with pentagastrin stimulation tests. Of the 21 family members screened, 10 were found to have the RET proto-oncogene mutation (codon 634, TGC-GGC; 5 females and 5 males; 6 adults and 4 children). Zirie et al. (2001) concluded that this family with MEN IIA showed classic Mendelian autosomal dominant inheritance.

Schulten et al. (2011) screened 13 sporadic and inherited MTCs and matched non-tumor specimens for possible mutations in the RET, HRAS, KRAS, NRAS, v-raf murine sarcoma viral oncogene homolog B1 (BRAF), v-akt murine thymoma viral oncogene homolog 1 (AKT1), and CTNNB1 (β-catenin) genes.  They identified RET mutations in seven of 13 MTCs: five RET-positive cases revealed a mutation in exon 16 (p.M918T) and two a mutation in exon 10 (p.C618S and p.C620S).  In four of the RET-positive cases, the mutation was inherited, out of which three were reportedly associated with a multiple endocrine neoplasia type 2 (MEN2) syndrome [MEN2A: p.C618S, MEN2A/familial MTC (FMTC): p.C620S, and MEN2B: p.M918T].