遺伝障害と遺伝レポートのジャーナル

Atypical Hypotonia-Cystinuria a New Case: Genotype-Phenotype, Description

Preka Evgenia, Ariane Paoloni-Giacobino, Frédérique Sloan-Béna, Paloma Parvex and Alexandra Wilhelm-Bals

“Hypotonia-cystinuria syndrome” (HCS) and “the 2p21 deletion syndrome” are two recessive contiguous gene deletion syndromes associated with cystinuria. The deletions differ in size and number of genes involved. HCS is characterized by hypotonia, failure to thrive, severe growth retardation, growth hormone deficiency, characteristic facial dysmorphy and cystinuria. In addition to mental retardation and respiratory chain complex deficiency, the 2p21 deletion syndrome presents HCS features. In HCS, SLC3A1 and PREPL genes are disrupted, while in the 2p21 deletion syndrome two additional genes (C2orf34 and PM1B) are deleted. Mutations in SLC3A1 are known to cause cystinuria. The extended phenotypes are attributed to PREPL and C2orf34 PM1B deletions. While HCS is described in 19 families, 2p21 syndrome is only in one Bedouin family. An intermediate phenotype, resulting from deletion of SLC3A1, PREPL and C2orf34 has been reported twice and is known as “atypical HCS”. We will describe a new case of “atypical HCS” and its genotype-phenotype correlation. Array-CGH evidenced a homozygote microdeletion in chromosome 2p21 partially including genes SLC3A1 and CAMKMT and complete inclusion of the PREPL gene. Both parents showed the same deletion in the heterozygous state. In contiguous deletion syndromes, characterization of the different deletions is crucial for precise genotype-phenotype correlation and to understand the role of each gene.