Complete mitochondrial sequences for haplogroups M23 and M46: insights into the Asian ancestry of the Malagasy population.

Through the sequencing of the complete mitochondrial genome of three individuals of Malagasy ancestry, we completed the characterization of the island southeastern Asian specific M46 haplogroup. We assumed that the association of the np 3588 and np 16278 polymorphisms were M46 specific. In addition, we characterized a novel basal M subhaplogroup: M23. This clade can be defined by one coding region transition at np 10295 and one control region transition at np 16263. Our data suggest the arrival of South Asian migrants before the start of the 15th century and highlights the fact that future studies dealing with the settlement of Madagascar should consider at least three potential source populations (Africa, Indonesia, and India).

Expanding the clinical spectrum of B4GALT7 deficiency: homozygous p.R270C mutation with founder effect causes Larsen of Reunion Island syndrome.

First described as a variant of Larsen syndrome in Reunion Island (LRS) in the southern Indian Ocean, 'Larsen of Reunion Island syndrome' is characterized by dwarfism, hyperlaxity, multiple dislocations and distinctive facial features. It overlaps with Desbuquois dysplasia, Larsen syndrome and spondyloepiphyseal dysplasia with dislocations ascribed to CANT1, FLNB and CHST3 mutations, respectively. We collected the samples of 22 LRS cases. After exclusion of CANT1, FLNB and CHST3 genes, an exome sequencing was performed in two affected second cousins and one unaffected sister. We identified a homozygous missense mutation in B4GALT7, NM_007255.2: c.808C>T p.(Arg270Cys) named p.R270C, in the two affected cases, not present in the unaffected sister. The same homozygous mutation was subsequently identified in the remaining 20 LRS cases. Our findings demonstrate that B4GALT7 is the causative gene for LRS. The identification of a unique homozygous mutation argues in favor of a founder effect. B4GALT7 encodes a galactosyltransferase, required for the initiation of glycoaminoglycan side chain synthesis of proteoglycans. This study expands the phenotypic spectrum of B4GALT7 mutations, initially described as responsible for the progeroid variant of Ehlers-Danlos syndrome. It further supports a common physiopathological basis involving proteoglycan synthesis in skeletal disorders with dislocations.