How history and geography may explain the distribution in the Comorian archipelago of a novel mutation in DNA repair-deficient xeroderma pigmentosum patients

Abstract

Xeroderma pigmentosum (XP) is a rare, genetic, autosomal nucleotide excision repair-deficient disease characterized by sun-sensitivity and early appearance of skin and ocular tumors. Thirty-two black-skinned XP from Comoros, located in the Indian Ocean, were counted, rendering this area the highest world prevalence of XP. These patients exhibited a new homozygous XPC mutation at the 3'-end of the intron12 (IVS 12-1G>C) leading to the absence of XPC protein. This mutation, characteristic of the consanguineous Comorian families, is associated with a founder effect with an estimated age of about 800 years. Analysis of mt-DNA and Y-chromosome identified the haplogroups of patients, who are derived from the Bantu people. Although the four Comorian islands were populated by the same individuals during the 7-10 th centuries, XP was found now only in the Comorian island of Anjouan. To avoid the slavery process caused by the arrival of the Arabs around the 11-13 th centuries, inhabitants of Anjouan, including XP-heterozygotes, hid inland of the island protected by volcanoes. This population lived with an endogamic style, without connection with the other islands. XP patients still live in the same isolated villages as their ancestries. Local history and geography may, thus, explain the high incidence of XP located exclusively in one island. SubjectsThe XP patients as well as some of their relatives were interviewed and examined by clinicians and geneti-

Clinical and Mutational Spectrum of Xeroderma Pigmentosum in Egypt: Identification of Six Novel Mutations and Implications for Ancestral Origins

“…The c.2251-1G>C mutation was reported as founder mutation in Comoros, Kenya, Mozambique, Zimbabwe, north of South Africa and Pakistan [ 42 , 51 , 52 , 53 ]. It was concluded that the c.2251-1G>C mutation arose 800 years ago in the Bantu population in West-Central Africa who migrated to the Comoro Islands and expanded East and South Africa given the oceanic crossroad nature of the Comoros between Bantu East Africa, the Middle East, the Red Sea, the Arabic Peninsula and southeast Asia [ 35 ]. One study identified c.2251-1G>C mutation in 47% of Brazilian XP patients suggesting a possible link to the Comorian ancestry via the travel Portuguese slave traders from the east coast of Africa, mostly Mozambique to Brazil [ 49 ].…”

“…Mutational profiling improves disease and molecular characterization, and can explain similar clinical outcomes through investigating common ancestries [ 12 , 33 , 34 , 35 , 36 ]. In the current study, we describe clinical and genetic findings of 36 Egyptian XP patients (XP5GI to XP40GI) with and without neurological abnormalities.…”

Intrafamilial Variability in <b><i>LPIN1</i></b>-Related Rhabdomyolysis

“…We report herein the first familial case of a young boy and his mother both affected by homozygous LPIN1 -related rhabdomyolysis. Inheritance seems pseudo-dominant, due to a probably highly consanguineous family and founder effect, which have already been mentioned for Comorian populations in other diseases [Sarasin et al, 2019]. The index case experienced a first extremely severe episode of acute rhabdomyolysis at 14 months of age and a lethal second episode at 3 years of age, whereas his mother had only a moderate episode of rhabdomyolysis in adulthood.…”

Comprehensive germline mutation analysis and clinical profile in a large cohort of Brazilian xeroderma pigmentosum patients

“…The most common variant, XPC c.2251‐1G>C (10 of 27 cases), was previously described as a founder mutation in 18 Comorian XP patients from the Mayotte population in East 15 and South Africa 19,20 . This variant was also reported in seven XP Pakistani families 21 .…”