Fecundity in an infertile man with r(15) – a challenge to the current paradigm

Ring chromosome 15 [r(15)] is a rare condition with a mild-to-severe growth failure, mental disabilities, café-au-lait spots, specific facial features, fertility difficulties and other minor dysmorphic stigmata. Of almost 50 affected individuals reported in the literature, none were assessed for the...

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Bibliographic Details
Published in:Reproductive biomedicine online 2018-02, Vol.36 (2), p.210-218
Main Authors: Kalantari, Hamid, Karimi, Hamideh, Almadani, Seyed Navid, Fakhri, Mostafa, Mokhtari, Pegah, Gourabi, Hamid, Mohseni Meybodi, Anahita
Format: Article
Language:English
Subjects:
Adult
Aged
Chromosomes, Human, Pair 15
Female
Humans
IGF1R
Infant, Newborn
Infertility
Infertility, Male - genetics
Inheritance Patterns
Karyotyping
Male
Mosaicism
PCSK6
Ring chromosome 15
Ring Chromosomes
SNRPA1
TM2D3
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Summary:Ring chromosome 15 [r(15)] is a rare condition with a mild-to-severe growth failure, mental disabilities, café-au-lait spots, specific facial features, fertility difficulties and other minor dysmorphic stigmata. Of almost 50 affected individuals reported in the literature, none were assessed for the precise breakpoint positioning, which creates uncertainty in defining a specific phenotype for the deleted segment. This study reports for the first time the vertical transmission of r(15) in three consecutive generations of a family, including a subfertile man, his mother and his newborn infant. Array comparative genomic hybridization results revealed a 563 kb deletion of 15q26.3, overlapping the OMIM genes SNRP1, PCSK6 and TM2D3. The hemizygosity was confirmed with real-time quantitative PCR. Regarding haploinsufficiency in 15q26.3, based on phenotypic characteristics of the carriers, the only rational conclusion is that SNRPA1, PCSK6 and TM2D3 are not gene-dosage sensitive and are probably inherited in an autosomal-recessive manner. Given growth deficiency in r(15) carriers, this shows that the growth retardation cannot be attributed entirely to IGF1R. The predominance of female patients with r(15) is the next as yet unanswered question; incomplete penetrance and/or variable expression of gene(s) in different genders may be involved, but further evidence is needed to support this idea.
ISSN:1472-6483
1472-6491
DOI:10.1016/j.rbmo.2017.10.115