Hypogonadotropic hypogonadism idiopathicGene: CLPP
Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is associated with a phenotype in OMIM and Gene2Phenotype (probable). There is currently not enough evidence to support a gene-disease association as the phenotypes among the patients vary. This gene has been given an Amber rating until more cases are available.
Created: 19 Jul 2021, 8:53 a.m. | Last Modified: 19 Jul 2021, 9:03 a.m.
Panel Version: 1.44
Comment on publications: PMID: 23541340, describes 3 consanguineous Pakistani families (PDF1, PKDF291 and DEM4395), all affected individuals had sensorineural hearing loss. Family PDF1: 3 affected sisters, 1/3 had delayed puberty, streak ovaries and hormone levels consistant with hypogonadotropic hypogonadism, 2/3 had incipient POF and 1/3 had white matter phenotype. All three had epilepsy, short stature, microcephaly (< 3 percentile), moderate learning difficulties and ataxia.
Family PKDF291: 4 affected females with primary amenorrhea and hypogonadotropic hypogonadism. 3/4 had rudimentary uterus and small ovaries, 1/4 had small uterus and normal sized ovaries. No learning disabilities, microcephaly, short stature, epilepsy or neurological deficiet in all affected females.
Family DEM4395: 1 affected male and 2 affected females. All females had normal periods but their hormone profiles were not investigated. Aside from hearing loss there were no other self reported medical problems.
PMID: 25956234. Consanguineous Saudi family with 1 affected male and 1 affected female. Both patients have hearing loss, growth retardation and mental retardation, spastic diplegia and mild-severe white matter loss. No seizures were described in the patients. There is a third sibling (8 months) with the same variant; however, he did not show any of the phenotypes seen in his siblings but he is under regular checkups from a clinical team.
PMID:26970254. Consanguineous family of Arabic descent. Proband with 4 unaffected siblings and parents. Proband has hearing loss, azoospermia, no neurological symptoms other than the foot drop (neurophysiology revealed a sensory-motor demyelinative axonal peripheral neuropathy of the lower limbs). Father has cerebellar ataxia (cause unknown).
PMID: 27087618. Non-consanguineous Turkish family; however, parents are from the same village. 2 affected siblings (1 male, 1 female). Sister has secondary amenorrhea, hearing loss, no ovaries detected, hypogonadotropic hypogonadism, no neurological problems. Brother has hearing loss but no other problems.
PMID: 27650058. Consanguineous Algerian family with 2 affected females. Both have hearing loss and secondary amenorrhea, but no other neurological symptoms.
PMID: 27899912. 3 affected families, with 5 affected individuals (all males). All had congenital deafness, psychomotor retardation, white matter phenotype and short stature. Patients were not tested for infertility.
Created: 7 Jun 2021, 12:30 p.m. | Last Modified: 7 Jun 2021, 12:30 p.m.
Panel Version: 1.149
Prominent white matter changes identified in at least three unrelated individuals.
Sources: Expert list
Created: 15 Sep 2020, 9:55 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Perrault syndrome 3, MIM# 614129
Variants in this GENE are reported as part of current diagnostic practice
Tag Q3_21_rating was removed from gene: CLPP. Tag watchlist tag was added to gene: CLPP.
gene: CLPP was added gene: CLPP was added to Hypogonadotropic hypogonadism idiopathic. Sources: Expert list,Expert Review Amber Q3_21_rating tags were added to gene: CLPP. Mode of inheritance for gene: CLPP was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CLPP were set to 27899912; 23541340; 25956234; 26970254; 27087618; 27650058 Phenotypes for gene: CLPP were set to Perrault syndrome 3, OMIM:614129